Hypogonadism

Question 1

Specific Clinical Manifestations of Hypogonadism

Answer 1

• incomplete or delayed sex development
• Reduced libido
• Dec body hair (less shaving)
• Infertility (low or no sperm count)
• Dec spontaneous erections
• Ht loss or dec bone density
• Hot flashes
• Gynecomastia

Question 2

Testosterone in Serum

Answer 2

free testosterone (1-3%)

albumin bound

SHBG (sex hormone binding globulin) bound (only free and albumin-bond are bioavailable)

Question 3

Screening

Answer 3

• 1- Morning total testosterone w/ mass spect (peak)
• 2- Confirm w/ repeat testing (b/c day-to-day variation)
• 3- Check free or bioavailable testosterone if total is low or suspect problem w/ SHBG (if dec SHBG then that may be falsely lowering total testosterone even though bioavailable testosterone is fine)
  - Can calculate manually
• **Only test if have clinical signs and symptoms
• **No accepted lower limit of normal to diagnose hypogonadism

Question 4

What causes inc and dec SHBG?

Answer 4

• Dec SHBG from … moderate obesity, nephrotic syndrome, acromegaly, hypothyroid, Type II DM, GCs/androgens/progestins
• Inc SHGB from .. aging, hepatitis or cirrhosis, estrogens, anti-convulsants, HIV, hyperthyroid

Question 5

How to determine primary v secondary hypogonadism?

Answer 5

• Look at FSH and LH
• If high … primary (testes not responding)
• If low or normal … secondary

Question 6

Causes of Primary Hypogonadism (overview)

Answer 6

• Congenital/ developmental - Klinefelter’s syndrome (XXY), Myotonic dystrophy, Uncorrected cryptorchidism, Noonan Syndrome, Bilateral congenital anorchia, Polyglandular autoimmune syndrome, Testosterone biosynthetic enzyme defects, Congenital Adrenal Hyperplasia (CAH), Complex genetic syndromes, Down syndrome, LH receptor mutation
• Acquired - Bilateral surgical castration or trauma, Drugs (spironolactone, ketoconazole, alcohol, chemotherapy agents), Ionizing radiation, Orchitis
• Systemic Disorders - Chronic liver disease (hepatic cirrhosis), Chronic kidney disease, Aging, Malignancy (lymphoma, testicular cancer), Sickle cell disease, Spinal cord injury, Vasculitis, Infiltrative disease (amyloidosis, leukemia)

Question 7

Causes of Secondary Hypogonadism (overview)

Answer 7

• Congenital/ developmental - Hemochromatosis, Constitutional delayed puberty, Idiopathic Hypogonadotropic Hypogonadism (IHH) including Kallman’s syndrome and Isolated LH deficiency; Complex genetic syndromes
• Acquired - Hyperprolactinemia, Opiates, Androgenic anabolic steroids, Progestins, Estrogen excess, GnRH agonist or antagonist, Hypopituitarism, Pituitary or hypothalamic tumor, Surgical hypophysectomy, Pituitary or cranial irradiation, Vascular compromise, Traumatic brain injury, Granulomatous or infiltrative disease, Infection, Pituitary stalk disease, Lymphocytic hypophysitis
• Systemic Disorders - Glucocorticoid excess, Chronic organ failure (liver, kidney, lung, heart), Chronic systemic illness (Diabetes mellitus, Malignancy, Rheumatic disease, HIV disease), Starvation, Malnutrition, Eating disorders, Endurance exercise, Morbid obesity, Obstructive sleep apnea, Acute and critical illness, Aging, Spinal cord injury, Transfusion-related iron overload, Sickle cell disease, Cystic fibrosis

Question 8

Klinefelter

Answer 8

XXY

Confirm w/ karyotype

Question 9

Orchitis

Answer 9

• most common manifestation of Mumps in pubertal boys and adults
• Permanent seminiferous tubule damage, impaired spermatogenesis, and, in severe cases, Leydig cell failure and androgen deficiency
• Mumps = headache, fever, and malaise followed by unilateral or bilateral parotid swelling due to parotiditis
• Then testis pain and swelling 10 days to 6 wks later (can be subclinical)

Question 10

Hemochromatosis

Answer 10

• iron overload in pituitary leads to gonadotropin def (may also have iron in testes themselves)

Question 11

Anabolic Steroid Use

Answer 11

• synthetic androgens dec HPA axis (neg feedback) –> low sperm counts
• Synthetic testosterones do not show up on assays; so can detect low actual testosterone in serum
• Usually do not present until stop using b/c synthetics prevent androgen deficiency symptoms

Question 12

GnRH Analog Use

Answer 12

used for prostate cancer and early puberty; suppress HPA axis too

Question 13

4 Forms Testosterone Replacement

Answer 13

• Testosterone ester IM injections every 1-2 wks; more fluctuations in level
• Testosterone gel - easier to apply and smoother levels; may not use if around children b/c can be transferred to others
• Testosterone patches - smoother levels but skin irritation more common than w/ gel
• Buccal testosterone - every 12 hrs; mouth irritation and alters taste

Question 14

Risks of Testosterone Replacement (6)

Answer 14

• Reduced sperm production; dec fertility
• Risk of metastatic prostate cancer; screen
• Gynecomastia
• Can induce or worsen obstructive sleep apnea
• Erythrocytosis - stimulates erythropoiesis (can inc stroke, clot, MI)
• Acne/ oily skin