Correspondence
Endocrine Effects of HIV Infection
N Engl J Med 1993; 328:889-890March 25, 1993
- Article
To the Editor:
Grinspoon and Bilezikian state (Nov. 5 issue)1 that “There is no evidence that pentamidine administered by aerosol alters pancreatic function.” At least three cases of pancreatitis,2,3 one of hypoglycemia,4 and two of diabetes mellitus5,6 have been reported after treatment with aerosolized pentamidine. Pentamidine can be absorbed systemically after being inhaled in aerosol form, although plasma levels are usually low7. Potential predisposing conditions include previous subclinical pancreatic damage, therapy with other drugs associated with acute pancreatitis (such as trimethoprim-sulfamethoxazole and didanosine), and overdosing of pentamidine administered by aerosol due to problems with nebulizer use. . . .
7 ReferencesEsteban Martinez, M.D.
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, SpainCarmen Martinez-Chamorro, M.D.
Elena Martinez-Chamorro, M.D.
Facultad de Medicina, 47010 Valladolid, Spain1
Grinspoon SK ,Bilezikian JP . HIV disease and the endocrine system. N Engl J Med 1992;327:1360-1365
Full Text | Web of Science | Medline2
Herer B ,Chinet T ,Labrune S ,Collignon MA ,Chretien J ,Huchon G . Pancreatitis associated with pentamidine by aerosol. BMJ 1989;298:605-605
CrossRef | Web of Science | Medline3
Hart CC . Aerosolized pentamidine and pancreatitis. Ann Intern Med 1989;111:691-691
Web of Science | Medline4
Karboski JA ,Godley PJ . Inhaled pentamidine and hypoglycemia. Ann Intern Med 1988;108:490-490
Web of Science | Medline5
Fisch A ,Prazuck T ,Malkin JE ,Patey O ,Lafaix C ,Leblanc H . Diabetes mellitus in a patient with AIDS after treatment with pentamidine aerosol. BMJ 1990;301:875-875
CrossRef | Web of Science | Medline6
Chen JP ,Braham RL ,Squires KE . Diabetes after aerosolized pentamidine. Ann Intern Med 1991;114:913-914
Web of Science | Medline7
Monk JP ,Benfield P . Inhaled pentamidine: an overview of its pharmacological properties and a review of its therapeutic use in Pneumocystis carinii pneumonia. Drugs 1990;39:741-756
CrossRef | Web of Science | Medline
To the Editor:
In discussing drugs that cause hypocalcemia, Drs. Grinspoon and Bilezikian mention ketoconazole and foscarnet. Intravenous pentamidine1,2 and the concurrent administration of pentamidine and foscarnet3 have also been reported to cause severe hypocalcemia in patients with AIDS.
Hypocalcemia induced by intravenous pentamidine was associated with marked hypomagnesemia in both reports,1,2 and it persisted even after the drug was stopped,2 probably a consequence of accumulation in renal tissue4. The hypomagnesemia was due to renal magnesium wasting, but the exact mechanism of pentamidine nephrotoxicity leading to urinary magnesium loss remains unknown. The serum levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol remained within normal limits in the patient described by Shah et al1.
4 ReferencesJai Chakrabarti, M.D.
Veterans Affairs Medical Center, Boston, MA 021301
Shah GM ,Alvarado P ,Kirschenbaum MA . Symptomatic hypocalcemia and hypomagnesemia with renal magnesium wasting associated with pentamidine therapy in a patient with AIDS. Am J Med 1990;89:380-382
CrossRef | Web of Science | Medline2
Burnett RJ ,Reents SB . Severe hypomagnesemia induced by pentamidine. DICP 1990;24:239-240
Medline3
Youle MS ,Clarbour J ,Gazzard B ,Chanas A . Severe hypocalcemia in AIDS patients treated with foscarnet and pentamidine. Lancet 1988;1:1455-1456
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Sands K ,Kron MA ,Brown RB . Pentamidine: a review. Rev Infect Dis 1985;7:625-634
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To the Editor:
Grinspoon and Bilezikian do not mention the association between megestrol acetate and hyperglycemia that has been described in patients with AIDS.1 We recently saw a 38-year-old cachectic man with AIDS who had been taking megestrol acetate for 11 months when hyperglycemia and an elevated C-peptide level developed, requiring insulin therapy. He was taking no other medications known to induce glucose intolerance. The megestrol acetate was stopped, and he became euglycemic without insulin therapy. The elevated C-peptide level suggests insulin resistance as the cause of the hyperglycemia; this is consistent with a proposed hypothesis for megestrol acetate-induced hyperglycemia.1 Physicians should be alert to this possible complication, because of the use of megestrol acetate to stimulate nutrient intake in patients with AIDS.
(The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.)
1 ReferencesMichael Bornemann, M.D., Col., M.C.
Arthur C. Johnson, III, M.D.
Tripler Army Medical Center, Tripler A.M.C., HI 968591
Henry K ,Rathgaber S ,Sullivan C ,McCabe K . Diabetes mellitus induced by megestrol acetate in a patient with AIDS and cachexia. Ann Intern Med 1992;116:53-54
Web of Science | Medline
To the Editor:
Under the heading “gonadal function,” Grinspoon and Bilezikian claim that information is available only for men. Unfortunately, this type of assertion underscores the pervasive exclusion of women as research subjects.
The authors state that men with human immunodeficiency virus (HIV) infection may report decreased libido and hair loss. This links anecdotal findings in men with possible hormonal dysfunction. In fact, there is no lack of similar anecdotal information about hormonal and immunologic dysfunction in HIV-positive women.
Clinicians who care for women with HIV infection have been reporting protracted gynecologic infections and menstrual dysfunction for several years.1 Of course, women also report decreased libido and hair loss, among other symptoms. In regard to decreased libido, depression must be considered as well as hormonal changes. As for hair loss, general malnutrition, chronic illness, and the possible effects of the use of zidovudine (Retrovir) or other medications must be added to the differential evaluation. Menstrual dysfunction may result from malnutrition, weight loss, the use of “street” drugs, antiviral agents, or HIV itself. Gynecologic infections and cancers may be related to local immune factors in the female reproductive tract. . . .
Although we must remain impartial about the results of scientific inquiry, we must not fail to recognize that it is our curiosity and concern for the well-being of all our patients that must direct the course of that inquiry. Until issues of concern to women with HIV disease or AIDS and their clinicians can be rendered visible to the scientific community, the support and resources needed to conduct the proper research into these questions will not be forthcoming.
1 ReferencesRisa Denenberg, F.N.P.
Bronx Lebanon Hospital Center, Bronx, NY 104561
Allen MH . Primary care of women infected with the human immunodeficiency virus. Obstet Gynecol Clin North Am 1990;17:557-569
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Author/Editor Response
The authors reply:
To the Editor: Aerosolized pentamidine is a relatively new form of prophylaxis and therapy for Pneumocystis carinii pneumonia in HIV-infected patients. No complications of dysglycemia or pancreatitis were reported in two early1,2 and one recent3 study of aerosolized pentamidine. Martinez et al. note recent case reports of such complications. A recent report on aerosolized pentamidine4 described two cases of pancreatitis, but other predisposing factors may have contributed. Given the low systemic levels of pentamidine associated with its use in aerosolized form,5 few if any side effects would be expected. We agree, however, that aerosolized pentamidine has the potential to cause some of the same side effects associated with its systemic administration.
Chakrabarti notes a complication of hypomagnesemia due to intravenous pentamidine. Renal magnesium wasting due to pentamidine may account for the hypomagnesemia.
Bornemann and Johnson describe two cases of hyperglycemia in association with the administration of megestrol acetate. It is important to evaluate the potential side effects of new therapies for aspects of HIV disease.
We agree with Denenberg that more research is needed on HIV infection in women. Women now represent an increasing percentage of those infected with the virus. They will clearly be subject to manifestations that are both similar to and different from those seen in men. The hypothalamic-pituitary-ovarian axis is a potential target and needs intensive study.
5 ReferencesSteven K. Grinspoon, M.D.
John P. Bilezikian, M.D.
Columbia University College of Physicians and Surgeons, New York, NY 100321
Conte JE ,Hollander H ,Golden JA . Inhaled or reduced-dose intravenous pentamidine for Pneumocystis carinii pneumonia: a pilot study. Ann Intern Med 1987;107:495-498
Web of Science | Medline2
Montaner JSG ,Lawson LM ,Gervais A , et al. Aerosol pentamidine for secondary prophylaxis of AIDS-related Pneumocystis carinii pneumonia. Ann Intern Med 1991;114:948-953
Web of Science | Medline3
Schneider MME ,Hoepelman AIM ,Eeftinck Schattenkerk JKM , et al. A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. N Engl J Med 1992;327:1836-1841
Full Text | Web of Science | Medline4
Hardy WD ,Feinberg J ,Finkelstein DM , et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med 1992;327:1842-1848
Full Text | Web of Science | Medline5
Monk JP ,Benfield P . Inhaled pentamidine: an overview of its pharmacological properties and a review of its therapeutic use in Pneumocystis carinii pneumonia. Drugs 1990;39:741-756
CrossRef | Web of Science | Medline
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