Case Presentation

1
Case Presentation

• Robert Comer, MD
• September 24th, 2007

2
Case

• E.R. is a 49 yo HIV and Hep C positive male
• Presented with bilateral breast enlargement
  approx 2 weeks after starting efavirenz/emtricitab
  ine/tenofovir (Atripla)
• Diagnosed with HIV 2002
• Had previously taken meds inconsistently

3
Case

• PMH Hep C type 1B, sinusitis
• Meds atripla
• PSH none
• SH Denies current drugs, alcohol, smoking
  stable living environment, working, 7 month old
  baby
• ROS Breast enlargement, non-tender, bilateral,
  10 point ROS neg

4
Case

• PE AF, VSS
• Gen AAO x 3, NAD
• HEENT - anicteric, no thrush
• CV RRR w/o M/R/G Lungs CTA B
• Breast firm, moveable, breast nodule,
  enlargement, LgtR, Non-tender, no skin changes
• Abd, Skin, LAD, GU - WNL

5
Labs

• CD4 561 (251-561)
• Viral load remained undetectable
• 49 year old HIV, HCV positive with bilateral
  breast enlargement
• DDx?

6
Differential

• Lymphoma unlikely and rare
• Lipodystrophy
• Gynecomastia
• Breast CA

7
Lymphoma

• Lympadenopathy
• Abnormal CBC, LDH

8
Breast Cancer

• Weight loss
• Skin changes
• Breast tenderness
• 1 of total breast cancers are male

9
Lipodystrophy

• Fat redistribution
• Elevated TG, cholesterol
• Insulin resistance

10
Gynecomastia

• Proliferation of glandular ducts and periductal
  stroma
• Alteration in the ratio of effective estrogen to
  testosterone
• Diagnose by ultrasound, true vs. pseudo

CID 2002351113-19
11
(No Transcript)
12
Gynecomastia

• Physiologic puberty, obesity
• Endocrine acromegaly, chromophobe adenoma,
  adrenocortical adenoma/carcinoma, hyper or
  hypothyroidism
• Gonadal Kleinfelter syndrome, viral orchitis,
  granulomatous disease, primary or secondary
  hypogonadism
• Liver Disease Hepatitis, cirrhosis,
  hemochromatosis, hepatocellular carcinoma

13
Gynecomastia

• Tumors testicular germ cell tumor, Leydig-cell,
  Sertoli-cell, chroiocarcinoma, bronchial
  carcinoma, renal cell carcinoma, adrenal
• Drugs of abuse cannabis, amphetamines,
  methadone
• Medicines Hormones, androgen antagonists
  (sprionalactone, cimetidine, digitalis,
  griseofulvin), Prolactin stimulators
  (hydroxyzine, metoclopramide), INH, ketoconazole

14
Antiretrovirals and Gynecomastia

• Protease inhibitors Ritonavir
• Saquinivir
• Indinavir
• Nelfinavir

CID 199725937-7 CID 1998271539-40 CID 1998
261482
15
Antiretrovirals and Gynecomastia

• NRTI didanosine, stavudine
• Most frequent is didanosine

CID 2004 1514-19 AIDS19972167 AIDS 2004,
1347-9
16
Antiretrovirals and Gynecomastia

• NNRTI efavirenz, 5 cases, another with 16
• 4-28 months after starting
• Appropriate immunological and virological
  responses
• Resolved 5 months after withdrawal of efavirenz

Breast Jounal, 2004244-46 AIDS 2004, 181347-9
17
Antiretrovirals and Gynecomastia

• Mechanisms
• -Immune reconstitution
• -estradiol-like effects of medicines
• May be associated with lipodystrophy syndrome
• Incidence is 2.8 on HAART (1.8-5.1)

Breast J 2004244-246 AIDS Read 2000703-708
AIDS Res Human Retrovirus 2003739-41 Scandinavia
JID 2001559-60 CID 20041514-19
18
Case

• 49 year old male with breast enlargement,
  Differential
• Lymphoma
• Breast CA
• Lipodystrophy
• Gynecomastia

19
Work Up

• Lipodystophy syndrome LDL 45, TG 191, glucose
  99
• Lymphoma No LAD, CBC WNL
• Breast CA ultrasound neg for cancer
• Gynecomastia ultrasound positive for true
  gynecomastia

20
Work Up

• Gynecomastia
• Endocrine Thyroid, adrenal, pituitary
• Gonadal failure primary and secondary,
  testicular tumor
• Liver disease HCV, hepatocellular carcinoma
• Renal disease
• Drugs - efavirenz

Int J Clin Pract 2007, 611209-15
21
Work up

• Endocrine TSH 1.90, prolactin 15.5 (4-15.2)
• Drugs just started Atripla, unlikely this
  early, usually unilateral
• Liver disease AST 79, ALT 78, AFP 2.9
• Renal failure BUN, creat WNL, UA w/o hematuria
• Testicular tumor no masses

22
Work up

• Hypogonadism total testosterone 393 (WNL)
• Free testosterone 2.59 (4-16)
• LH 15.7 (1.7-8.6)
• Estradiol 47 (8-43)

23
Primary Hypogonadism

• Increased FSH and LH stimulate aromatase release
• Aromatase converts testosterone to estradiol
• Often leads to gynecomastia
• Higher incidence in patients with HIV not on
  HAART, although secondary more common

Metabolism 1995, 4596 CID 2004, 391514-19
JAMA 2007, 3571229-37
24
Treatment of Gynecomastia

• Glandular tissue gets replaced by fibrosis, so
  rapid correction is best
• Remove the medicine
• Tamoxifen
• Anti-aromatase inhibitors coming
• Testosterone
• Surgery
• Often resolve on their own

J Clin Endo Metab 1971, 32173-8 Metabolism
1986, 35705-8 South Med J 1990, 831283-5
Acta Endo Suppl 1986, 279218-26
25
Summary

• Isolated gynecomastia can present in patients
  with HIV
• Determining etiology takes a careful and thorough
  investigation
• Can be associated with HAART therapy
• Often times is not