December 2019 • VOL. 67                                                                           Supplement to JAPI • December 2019

Case Report

HAART Induced Gynaecomastia

Mahesh Dave¹, Lavanya SR², Manoj Patidar³, Prateek Bapat⁴, Mukesh Jiterwal⁴, Kaptan Yadav⁵, Shibsankar Sarkar²

1Professor Medicine, 2Junior Resident 1, 3Asst. Professor Medicine, 4Junior Resident 2, 5Junior Resident 3, RNT Medical College, Udaipur, Rajasthan

Abstract

Benign glandular enlargement of male breast is called gynaecomastia.Various drugs have been implicated as the cause. Most widely used HAART regimen TLE is enlisted in least common cause of gynaecomastia. A 42 yr old male diagnosed HIV seropositive since last 10 yrs was put on TLE regimen and he presented with gynaecomastia since 11 months. We hereby report this finding on HAART.

Introduction

Gynaecomastia results from proliferation of glandular component of breast. The prevalence of male gymaecomastia is 35-45%. It is frequent during three phases in the age distribution curve: the neonatal period, pubertal period and sene scence . The prevalence of asymptomatic gynecomastia in neonates is estimated to be between 60 and 90%. The second physiological peak of occurrence is at puberty between the ages of 10 and 16 years. Approximately 50–60% of adolescents have been estimated to have gynecomastia based upon early literature.1 In adult males it is often multifactorial. Out of all causes of male gynaecomastia,drug induced contributes to 25-30%. The important drugs includes in the list are anti-emetics, phenothiazines, anti-hypertensives , H+K+ pump blockers etc.2 Anti-retroviral drugs like Lamivudine, Efavirenz may be associated with Gynaecomastia and are rare.

Case Report

A 42 yr old male was admitted in our ward with complaints of bilateral breast enlargement for last 11 months, which was progressive and painless (Figure 1). He was diagnosed HIV seropositive 10 yrs back and was put on Tenofovir, Lamivudine, Effavirenz (TLE) regimen. There was no significant h/o intake of drugs causing gynaecomastia. There was no significant h/o blurring of vision, diplopia, decreased sensation of smell, distention of abdomen, increased sweating, palpitation, weight loss and loss of appetite. On further enquiry of the patient, there was no history suggestive of hypogonadism, chronic liver disease, thyroid dysfunctioning etc. Patient was a non-alcoholic and occasional smoker with no other illicit drug habits. He is a farmer by occupation with no family h/o gynaecomastia.

On physical examination patient was conscious and oriented to time, place and person. He was well built with weight being 65 kgs, height being 170 cm and BMI 22.5 kg/m2. Vital parameters were found to be normal.
On local examination there was bilateral enlargement of breast which was soft to firm in consistency, nontender, without any nipple-areolar complex changes and discharge. Overlying skin was normal without any engorged veins, thus it was graded as Stage 3 gynaecomastia (Simon et al study 1973). There was no significant lymphadenopathy. His abdominal examination including testicles were within normal limits. His secondary sexual characters such as pubic hair, axillary hair were found to be normal. Other systemic examination revealed no abnormality.
This patient was extensively investigated to establish the primary cause and to rule out all other secondary causes of gynaecomastia. His routine blood investigation like CBC, RFT, LFT were within normal limits. Chest X-ray and ECG revealed no abnormality. CD4 count were 104/ microlitre. Specific investigation like serum Prolactin was 10.53 ng/ml, serum FSH 7.2 mIU/ml, serum LH 17.77 mIU/ml, serum testosterone, estrogen, progesterone were within normal limit, thyroid function were within normal limit. USG of both breast was showed mixed intensity which simulates mammary tissue, suggestive of bilateral gynaecomastia. FNAC of both breasts was done and was showing benign ductal cells round oval in shape and arranged in clusters with background proliferation of fibrolipomatous tissues (gynaecomastia) (Figure 2). Mammography of both breast done and was suggestive of benign lesion ( gynaecomastia ) ( Figure3 ) . MRI Brain for pituitary and hypothalamus revealed no abnormality.

Discussion

Gynecomastia , aglandular proliferation in the male breast, is a common clinical condition that may occur in males of all ages. Gynecomastia is derived from the Greek terms gynec ( female ) and mastos (breast) and was first coined by Galen in the second century AD. It can be unilateral, bilateral, and/or asymmetrical.Gynecomastia may cause significant embarrassment and psychological distress in affected males.3
The mechanisms underlying the development of HAART - induced gynaecomastia are not exactly clear. It has been suggested that improvements in T-ce l l cytokines, par t i cularly interleukin-2 (IL-2) response may influence the growth of breast tissue after commencement of an effective HAART regimen. IL-2 has been shown to increase the proliferation of breast carcinoma cells in vitro. In addition, Interleukin-6 (IL-6) increases the availability of estrogen and stimulates breast growth, thus raising the possibility of an immune restoration process (Qazi et al., 2002). Antiretroviral agents inhibit cytochrome P-450 which may elevate the estrogen-androgen ratio. Decreased estrogen metabolism, displacement from estrogen-binding globulin, and diminished testosterone biosynthesis has also been postulated as possible mechanisms leading to gynaecomastia. However, estradiol levels in our patients were not elevated. Decreased oestrogen metabolism, displacement from oestrogen-binding globulin, and diminished testosterone biosynthesis has also been postulated as possible mechanisms leading to gynaecomastia.4 Efavirenz directly modulates the oestrogen receptor and induces breast cancer cell growth in experimental models. Similar type of case reports with HAART regimen ( Efavirenz / Lamivudine ) induced gynaecomastia has been reported in literature.5

Conclusion

In Indian population, gynaecomastia is a rare entity in HIV infected men receiving TLE based HAART regimen and careful attention should be paid to the long-term follow-up of these patients.

References

1. Sabiston Textbook of Surgery 18th ed 2008 publication

2. Harrison Principles of Internal Medicine 19th ed page 2365

3. Journal of Medicine and Medical Sciences 2011; 2:1221-1224.

4. Paech J, Lorenzen T, von Krosigk A, Graefe K, Stoehr A, Plettenberg A. Gynaecomastia in HIV-infected men: association with effects of antiretroviral therapy. AIDS 2002; 16:1193-1194.

5. Rama SK, et al. The Southeast Asian Journal of Case Report and Review July-Aug 4(4) ISSN: 2319-1090 Page 1901.