Endocrine Testing. Alice Y.Y. Cheng, MD, FRCP October 14, 2015

Transcription

1 Endocrine Testing Alice Y.Y. Cheng, MD, FRCP October 14, 2015

2 Disclosure No disclosures relevant to the content of this workshop

3 Learning Objectives By the end of this workshop, you will be able to: 1. Utilize appropriate testing for thyroid nodules 2. Develop an approach to the incidental adrenal nodule 3. Order and interpret initial investigations for a pituitary incidentaloma

4 Ms. BC 20 year old woman Noted a lump in her neck Corresponds with a thyroid nodule on physical examination

5 Differential diagnosis Benign Colloid Hyperplastic Functional adenoma Cysts Malignant Papillary, follicular, medullary, anaplastic, lymphoma Cooper DS et al. Thyroid 2009;19(11):

6 What are key history features? Onset, rapidity of growth? Obstructive / compressive symptoms? Dyspnea, dysphagia, stridor Voice hoarseness Function? (hyper or hypo) Cooper DS et al. Thyroid 2009;19(11):

7 Risk Factors for malignancy Age (< 20 or >65) Sex (M > F) Radiation history Cancer treatment, BMT Environmental (Chernobyl) Acne, tonsils Family history of thyroid cancer Rapid growth, hoarseness Ethnicity? Cooper DS et al. Thyroid 2009;19(11):

8 Risk Factors for malignancy Size (> 4 cm) Fixed Hard Lymphadenopathy Vocal cord paralysis Cooper DS et al. Thyroid 2009;19(11):

9 Investigations TSH (functional?) Functional nodules are BENIGN Cooper DS et al. Thyroid 2009;19(11):

10 Nuclear Medicine tests NOT necessary in most cases! Uptake: Test of FUNCTION and not structure Useful if HYPERTHYROID Scan: Test of STRUCTURE and not function Useful if HYPERTHYROID and NODULE Only useful finding = hot Cooper DS et al. Thyroid 2009;19(11):

11 Risk stratification by U/S HIGH MEDIUM LOW VERY LOW BENIGN Hypoechoic with irregular margins Microcalcifications Taller > wide Interrupted rim calcification Suspicious lymph node Hypoechoic solid nodule with regular margins Hyperechoic or isoechoic solid nodule with regular margins Partly cystic with eccentric solid component Spongiform Cystic with benign-looking solid component Simple cyst 2015 American Thyroid Association guidelines (in press).

12 U/S Patterns and FNA Suggestions U/S Patterncancer risk Est cancer risk Threshold for FNA Strength High 70-90% 1 cm Strong Intermediate 10-20% 1 cm Strong Low 5-10% 1.5 cm Weak Very Low <3% 2 cm Weak Benign <1% No FNA Strong Do NOT biopsy any nodule < 1 cm Strong Modify cutoffs based on risk factors, suspicious lymph nodes 2015 American Thyroid Association guidelines (in press).

13 Multiple nodules and FNA When multiple nodules > 1 cm are present, FNA based on US pattern If multiple similar low or very low risk nodules are present, it is reasonable to FNA the largest ( over 2 cm) and observe the others 2015 American Thyroid Association guidelines (in press).

14 FNAB results 1. Malignant = surgery 2. Benign = follow 3. Indeterminate = surgery 4. Inadequate = repeat FNAB

15 F/U of benign cytology US- guided FNA has a very low false negative rate US pattern Strength High suspicion Repeat US and FNA in 12 mo Medium/low suspicion Very low suspicion Repeat US mo, if growth* repeat FNA or observe Utility unknown- if repeated, wait >24 mo If a second FNA is benign, US surveillance is NOT indicated Strong Weak None Strong * Growth defined as 50% increase in volume, or 20% increase in dimensions 2015 American Thyroid Association guidelines (in press).

16 F/U if NOT initially biopsied US pattern Strength High suspicion Repeat US in 6-12 mo Weak Medium/low suspicion Very low suspicion Repeat US mo Utility unknown- if repeated, wait >24 mo Nodules < 5 mm do not require routine US followup Weak No rec Weak 2015 American Thyroid Association guidelines (in press).

17 Ms. BC 20 year old woman 2.5 cm solid hypoechoic with reg margins No other risk factors for thyroid cancer Firm, mobile, no lymphadenopathy TSH 2.6 miu/l

18 Take home points Risk factors for malignancy radiation, family history, age, sex, Phillipino Size (>4cm), obstruction/compression Ultrasound features U/S, TSH, FNAB for almost all Uptake & scan ONLY if hyperthyroid Only investigate > 1-2 cm based on risk

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20 Mr CX 55M found incidentally to have a 1.5cm Left adrenal nodule on CT abdo Feels well PMH: hypertension well controlled Meds: ACE-inhibitor, CCB

21 Adrenal incidentaloma 8.7% incidence on autopsy series Is the tumour hormonally active? Radiologic features of malignancy? History of previous malignancy? Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

22 Differential Diagnosis Nonfunctioning adenoma (80%) Subclinical Cushing syndrome (5%) Pheochromocytoma (5%) Adrenocortical carcinoma (<5%) Metastatic lesion (2.5%) Aldosteronoma (1%) Ganglioneuroma, myelopimoa, benign cysts Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

23 History: r/o functional tumour Cushings: weight gain, centripal obesity, bruising, hypertension, diabetes, prox muscle weakness, fatigue Pheo: episodes of headache, sweating and palpitations, pallor, weight loss, anxiety, hypertension, family hx, Hyperaldo: uncontrolled HTN, hypok Met / cancer: weight loss, hx of cancer, smoking Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

24 Physical exam Rule out functional tumour Blood pressure Cushingoid appearance, ecchymoses, striae, wasting, hirsutism, virilization Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

25 Investigations 1mg overnight dexamethasone suppression test 24 hour urine metanephrines, catecholamines Electrolytes, renin, aldosterone Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

26 1 mg overnight Dex Day 1: 2300h take 1 mg Dexamethasone Day 2: 0800h measure CORTISOL Normal <50 nmol/l cortisol Caution with OCPs Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

27 24h urine catechols, metanephs Remember the creatinine Diet to follow before collection Meds to hold x 2 weeks before Tricyclics, levodopa, methyldopa, acetaminophen, decongestants, amphetamines, phenoxybenzamine Major stress Lenders WJM, et al. Lancet 2006;266:

28 Hyperaldosteronism Stop spironolactone, eplerenone, amiloride, HCTZ, licorice x 4 weeks Correct hypokalemia, eat high Na diet BB, methyldopa, clonidine, NSAID, ACE, ARB, DRI can also interfere High aldo, low renin adrenal vein sampling may be needed Funder JW et al. JCEM 2008;93:

29 Radiology Benign CT characteristics Homogenous Regular borders HU <10 <4cm Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

30 CT in 3-6m, 1y, 2y Hormonal test every year x 5y Growth = 1cm After 5 years? Zeiger MA et al.. Endocrine Practice 2009; 15(S1) :1-20.

31 Kapoor A et al. Can Urol Assoc 2011;5(4):241-7.

32 Mr CX 55M found incidentally to have a 1.5cm Left adrenal nodule on CT abdo Feels well PMH: hypertension well controlled Meds: ACE-inhibitor, CCB OE: BP 120/75 mmhg, nil else Investigations negative

33 Take home points Benign vs malignant/met Function vs non-function History and physical 4cm and CT features 1mg overnight dex 24h urine catechols, metanephrines Renin, aldosterone, potassium (if HTN)

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35 Ms DT 45F incidental finding of 9 mm pituitary tumour on imaging for headaches Referred to you for assessment

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37 Assess for 1. Hormone hypersecretion 2. Hormone hyposecretion 3. Compression / invasion of surrounding structures

38 Hormone Hyperfunction Hypofunction ACTH Cushing s syndrome (weight gain, central obesity, striae, prox muscle weak etc) Adrenal insufficiency (weight loss, fatigue, NO hyperpigmentation) GH FSH, LH TSH Prolactin Acromegaly (sweating, change features etc) Usually subunit so no symptoms Thyrotoxicosis ( TSH, ft4) Amenorrhea, low libido, ED, galactorrhea General fatigue, nonsepcific Amenorrhea, decreased libido, ED Hypothyroidism ( TSH, ft4) Nil to find clinically (no lactation postpartum)

39 Bitemporal hemianopsia CSF rhinorrhea Cranial nerve - ophthalmoplegia Di leva A et al. Nature Review Endocrinology 2014;10: c

40 Prolactin Investigations LH, FSH, estradiol / testosterone IGF-1 TSH, free T4 ACTH, morning cortisol (if suspect hypofunction) 1mg overnight dex suppression (if suspect Cushing s) VF testing if abutting the optic nerve or chiasm Freda PU et al. J Clin Endocrinol Metab 2011;96:

41 Freda PU et al. J Clin Endocrinol Metab 2011;96:

42 Refer for surgery Visual field deficit, vision problem, ophthalmoplegia Abut or compress optic chiasm or nerves Pituitary apoplexy with visual disturb Hypersecreting tumour (not prolactinoma) Loss of pituitary function Growth of the pituitary incidentaloma Unremitting headache Freda PU et al. J Clin Endocrinol Metab 2011;96:

43 Microadenoma Follow-up Annual MRI x 3 years then less often Macroadenoma Repeat MRI in 6 months then yearly x 3 years then less often Test for hypopituitarism in 6 months then yearly Freda PU et al. J Clin Endocrinol Metab 2011;96:

44 Ms DT 45F incidental finding of 9 mm pituitary tumour on imaging for headaches Only symptom is secondary amenorrhea Normal physical exam Labs: prolactin 88 mcg/l (4-24 mcg/l), LH low, FSH low, estradiol low. Rest all normal

45 Ms DT Diagnosis: Microprolactinoma Treatment: CABERGOLINE 0.5 mg 2x per week Repeat prolactin in 2-3 months Counsel about pregnancy plans

46 Take home points Hyperfunction? Hypofunction? Compression? Remember the hormones Remember the investigations Red flag: Any visual disturbance <1cm = micro 1cm = macro