Functional Low T Syndrome: Diagnosis and Treatment - PowerPoint Presentation

Slide1

Functional Low T Syndrome: Diagnosis and Treatment

David D’Alessio, MD

Director, Duke Endocrinology

Slide2

Objectives:

Describe the normal range for testosterone across the age spectrum

Understand the common clinical assays for testosterone and their

strengths and weaknesses

3. List the important adverse effects of testosterone replacement and

how to mitigate these

Slide3

54 year old male with

htn

and obesity and hyperlipidemia, on amlodipine and atorvastatin

who presents with complaints of diminished libido for the past 6 months.  He is married, in a good relationship, but works way too hard and is under moderate stress.  He enjoys several glasses of red wine each evening.

Key features on history

Features on exam

What labs?

Slide4

Definition of male hypogonadism

Syndrome

of decreased androgen effect (usually T production) and/or sperm production

Organic- disease of the gonads or pituitary

Functional- no clear etiology

Slide5

Testosterone assays: Being a smart (lab) shopper

Mass spectrometry- the Gold Standard (Mayo Gen Code)

- high precision and specificity

- free testosterone measured by dialysis

Conventional total T assays- RIA / ELISA (Duke lab)

- reasonable performance; good for monitoring

- total T is dependent on SHBG level

- can use TT and SHBG to estimate free T (Google lab)

3. Free T by analog immunoassays (Duke lab)

- inaccurate, poor reproducibility - not recommended… for anything

Slide6

Diagnosis of male hypogonadism

BDA

First

:

Measure total T (8AM is preferable)

-

Free T assays underestimate levels

Second

:

Repeat AM Total T with

FSH, LH and SHBG

-

Elevated FSH and LH = primary

Karyotype

-

Low/normal FSH and LH = secondary

Rule out hemochromatosis / hyperPRL

Review medications Rule out renal/hepatic, active CardioPulm dz Very low T (< 150 ng/dl) pituitary imaging

Mayo Clinic Total and Free testosteroneMass spectroscopy for total TEquilibrium Dialysis for free T

Two AM fasted blood draws:

Slide7

Testosterone secretion is diurnal

Slide8

54 year old male with

htn

and obesity and hyperlipidemia, on amlodipine and atorvastatin

who presents with complaints of diminished libido for the past 6 months.  He is married, in a good relationship, but works way too hard and is under moderate stress.  He enjoys several glasses of red wine each evening.

Key features on history- erections, # and success of sexual encounters

Exam- BMI = 32,

nl

secondary sexual characteristics, no gynecomastia, testes 15 cc

Labs:

Total T 216 Free T 3.8 Total T 206 PRL 11 TSH 1.2 FSH 4.3 LH 2.7 SHBG 18Key features on history- erections, # and success of sexual encounters

Exam- BMI = 32, decreased body hair, long arm/legs, bilat gynecomastia, testes 5 cc

Labs:

Total T 96 Free T 0.8

Total T 88 PRL 11 TSH 1.2 FSH 44.3 LH 42.7 SHBG 18

Slide9

Common causes of hypogonadism

Primary hypogonadism (10%)

Klinefelter’s syndrome

Secondary hypogonadism (90%)

Medical illness (COPD, CRF, ESLD, CHF, HIV, DM)

Medications (opiates, anti-psychotics, anti-depressants, corticosteroids)

Kallmann’s

syndrome (and other rare HP disorders)

Pituitary disease

Macroadenomas / Sellar mass lesionsHemochromatosisHyperprolactinemia

BDA

Slide10

NV is a 65 year old male, history of sleep apnea, obesity,

djd

, who was found to have

testosterone levels at low end of normal.  But, he complains of fatigue, decreased muscle mass, and says "things just aren't the same in the bedroom"... and follows that with "Hey doc, you have to start prescribing some T to help me!"

Do some men have symptoms of hypogonadism but their levels are within normal limits? 

If so, how do you approach them- what should be done?

b) Are there benefits to treating “Functional hypogonadism” in older men?

c) To further complicate things, we have heard that the FDA has indicated that testosterone

replacement or supplementation should only happen if specific pituitary or testicular disease

is documented.  So does that mean that this is not approved therapy for our aging males with symptoms and slightly low T levels and nothing else?

Slide11

The T Trials

PJ Snyder, Endo Rev 2018

Slide12

A Glass et al, JCEM 1977

S Harman et al, JCEM 2001

Common causes of apparent low testosterone

280

560

Slide13

Factors altering SHBG

Reduce SHBG

Obesity

Low protein (nephrotic)

Hypothyroidism

Steroids, progestins

Androgens,

anabolics

Raise SHBG

AgingCirrhosisHyperthyroidismHIVAniconvulsantsEstrogen

Slide14

Low testosterone secondary to Illness

Acute

Stress due to trauma or illness

Fasting, malnutrition

Steroids, opiates

Chronic

Renal, liver

dz

COPD, CHF

Wasting, inflammationObesity (BMI > 40)CNS active medicationsAnabolics, megace

Slide15

NV is a 65 year old male, history of sleep apnea, obesity,

djd

, who was found to have

testosterone levels at low end of normal.  But, he complains of fatigue, decreased muscle mass, and says "things just aren't the same in the bedroom"... and follows that with "Hey doc, you have to start prescribing some T to help me!"

Do some men have symptoms of hypogonadism but their levels are within normal limits? 

If so, how do you approach them- what should be done?

b) Are there benefits to treating “Functional hypogonadism” in older men?

c) To further complicate things, we have heard that the FDA has indicated that testosterone

replacement or supplementation should only happen if specific pituitary or testicular disease

is documented.  So does that mean that this is not approved therapy for our aging males with symptoms and slightly low T levels and nothing else?d) NV returns and has another testosterone level measured and its now mildly low, 15% below the lower limit of normal.  If you decide to treat him, what would you use and why?e) How should treatment be titrated and monitored?

Slide16

Treatment options

Injectable T

- 200 mg q 2 wks IM - 100 mg q

wk

SQ

- start low in young (prepubertal) and elderly

- monitoring is variable (and debatable)2. - Androgel pump (2-4 g / d) - titrate to total T level of 500 (timing of blood draw matters)

How to do a Subcutaneous Testosterone Injection - YouTube

Slide17

Common

Erythrocytosis

Acne

Fluid retention

Rare

Central apnea

Unknown

CAD

Prostate disease

BDA

Side effects of androgen replacement

Slide18

Precautions

Contraindicated:

Active or metastatic prostate cancer

Active breast cancerModerate risk of adverse outcomesHematocrit >50Severe lower urinary tract symptoms associated with benign prostatic hypertrophy as indicated by AUA/IPSS score >19

Uncontrolled or poorly controlled congestive heart failure

Slide19

Risks of androgen therapy on the prostate: Endocrinology and Mythology

Congenital hypogonadism = no prostate disease

Treated hypogonadism normalizes prostate & PSA

PSA restored to normal (no more than double)

No correlation: serum T levels & prostate disease

No



in prostate size or PSA in supraphysiologic T

T deprivation useful for pts with metastatic cancer

BDA

Slide20

PQ is a 73 year old male in good overall health, with some

djd

, mild

ckd stage 2, and htn.  He has moderately low testosterone level.  You want to treat him.   

What are some contraindications to treatment?  When should we NOT go ahead and write

the prescription?

If we do write the prescription, can we give a 90 supply?  Do you make everyone return

in 90 days, or can they request it in MyChart?c) How do you follow men over time on testosterone?  What labs should we be monitoring?

Slide21

Objectives:

Describe the normal range for testosterone across the age spectrum

Understand the common clinical assays for testosterone and their

strengths and weaknesses

3. List the important adverse effects of testosterone replacement and

how to mitigate these

Slide22

Case #1

A young couple are having difficulty conceiving a child and the male is referred for low

testostosterone

. He reports no low of libido and good sexual function. His wife had a spontaneous abortion 6 years ago. On exam, the young man has gynecomastia and very small testes. He is otherwise normal appearing and has a normal sense of smell.

Slide23

Small testes (2 cc) in man with

Klinefelters

Syndrome