- Email: [email protected]
Penile Gangrene: A Complication of Secondary Hyperparathyroidism from Chronic Renal Failure
0022-534 7/84/1326-1189$02.00/0 Vol. 132, December
THE JOURNAL OF UROLOGY
Copyright© 1984 by The Williams & Wilkins Co.
Printed in U.S.A.
PENILE GANGRENE: A COMPLICATION OF SECONDARY HYPERPARATHYROIDISM FROM CHRONIC RENAL FAILURE FRANKLIN C. LOWE
AND
CHARLES B. BRENDLER
From the Department of Urology, The Johns Hopkins University School of Medicine, James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland
ABSTRACT
We present the third case and first reported survivor of penile gangrene due to secondary hyperparathyroidism from chronic renal failure. The patient was treated with distal penectomy and subtotal parathyroidectomy. This case stimulated us to review the metabolic and vascular changes associated with secondary hyperparathyroidism in chronic renal failure. Secondary hyperparathyroidism may cause diffuse vasculitis and vascular calcification, which can lead to widespread ischemic necrosis and gangrene. Early medical therapy, including oral phosphate binders, is crucial to maintain the serum calcium-phosphate product below precipitation level. Subtotal parathyroidectomy is indicated for patients in whom progressive arterial and soft tissue calcification develops despite medical therapy. Gangrene of the penis can result from a variety of causes, including tourniquet syndrome,1 priapism, 2 •3 infection, 4 •5 venous thrombosis, 6 • 7 warfarin therapy8 • 9 and azotemic secondary hyperparathyroidism. 10• 11 We present the third reported case and the first survivor with penile gangrene from azotemic secondary hyperparathyroidism. The remaining 2 patients died of overwhelming sepsis. This case provided the impetus to review the metabolic and vascular changes that result from secondary hyperparathyroidism due to chronic renal failure. Since urologists and transplant surgeons frequently treat patients with end stage renal disease it is important to be aware of these problems. CASE REPORT
W. S., a 60-year-old white man with adult onset insulindependent diabetes mellitus and chronic renal failure, presented with dry gangrene of the penis in December 1983. The diabetes had been well controlled with 24 units of neutral protein Hagedorn insulin daily since 1960. The patient had renal insufficiency secondary to Kimmelstiel-Wilson disease, with a stable serum creatinine level of 4.0 mg./dl. until February 1981, when right radical nephrectomy was done for stage I renal cell carcinoma. Postoperatively, the serum creatinine increased to 8.0 mg./dl. and progressive renal failure ensued. Hemodialysis was begun in June 1983 via an arterial venous fistula in the left forearm. Painful cyanosis of the left fingers developed while the patient was on hemodialysis. This condition was attributed to arterial steal and peritoneal dialysis was started in November. Shortly thereafter the patient suffered dry gangrene of several fingers and toes. Two painful blisters arose on the glans penis that soon ulcerated. Biopsy of the penile ulcers revealed necrotic tissue only with no evidence of malignant, fungal or granulomatous disease. The 2 ulcers became progressively necrotic and within 4 weeks the entire glans was a dry gangrenous eschar. Initial management was conservative because of patient concern over the ability of a surgical incision to heal. However, penile pain became uncontrollable even with narcotics and the patient was referred to the urology service for evaluation. At that time the glans penis was a black, hard eschar with a pinpoint meatal opening (fig. 1). The proximal penile shaft was indurated but appeared viable. Doppler evaluation of the penis revealed no arterial pulsations. Shoddy bilateral inguinal adenopathy was noted. Other areas of dry gangrene included the Accepted for publication August 2, 1984.
left great toe, left index finger, left fifth finger and the right index finger. All 10 fingers were cyanotic. The right radial, right posterior tibialis, left dorsalis pedis and left posterior tibialis pulses were absent. Significant laboratory data included serum calcium 9.0 mg./ dl. (8.5 to 10.5 mg./dl.), phosphate 8.5 mg./dl. (2.5 to 4.5 mg./ dl.), alkaline phosphatase 240 mu./ml. (11 to 87 mu./ml.), parathyroid hormone levels intact 1,103 pg./ml. (7 to 330 pg./ ml.) and n-terminal 1,370 pg./ml. (230 to 630 pg./ml.). The serum calcium-phosphate product was 76.5 mg./dl. (60 to 75 mg./dl.). Radiographs of the extremities showed marked periosteal resorption as well as extensive calcification of the small and medium-sized vessels. Distal penectomy was performed to control the pain, and to prevent the development of progressive gangrene and cellulitis. During the procedure there was minimal bleeding from the skin, subcutaneous tissues and corpora cavernosa, both of which were thrombosed. The dorsal penile artery was calcified completely. Postoperatively, the patient immediately was rendered free of pain for the first time in 3 months. Five days after partial penectomy subtotal parathyroidectomy with removal of 3½ hyperplastic glands was performed with the hope of stabilizing the generalized vascular deterioration and to promote healing of the penile wound. Postoperatively, the digital cyanosis resolved promptly and the penis healed completely within 3 weeks. Serum calcium decreased to 5.6 mg./dl. but was stabilized with oral calcium and vitamin D supplements. Subsequently, the gangrenous left index and fifth fingers were amputated. A left below-the-knee amputation also was performed because of failure to heal an ankle and foot ulcer. Presently, the patient continues on peritoneal dialysis in stable condition without any new areas of gangrene. DISCUSSION
Manifestations of altered calcium metabolism occur com monly in patients with end stage renal disease. Renal osteodystrophy occurs early in about 25 per cent of the patients with chronic renal failure. As many as 80 per cent of the patients on long-term hemodialysis have soft tissue calcifications and bony abnormalities. 12 Soft tissue calcifications most commonly are arterial but ocular, periarticular, visceral and cutaneous involvement also occur. 13 Arterial calcification occurs in approximately 20 per cent of the patients in the early stages of chronic renal failure and up to 75 per cent of those with advanced secondary hyperparathyroidism. 14 Secondary hyperparathy-
1189
1190
LOWE AND BRENDLER
FIG. 2. Cross-sectional photomicrograph shows intraluminal calcifications (arrow) in dorsal penile artery. Reduced from X60. FIG. 1. Preoperative photograph demonstrates gangrenous glans penis with viable penile shaft.
roidism and its manifestations usually resolve after successful renal transplantation. 15 However, renal osteodystrophy, metastatic calcification and lethal calcinosis can occur after transplantation. 11 • 15 Arterial and metastatic soft tissue calcification in patients with uremia results from secondary hyperparathyroidism with high parathyroid hormone levels, hyperphosphatemia and connective tissue changes. 13 Three mechanisms are responsible for the increased parathyroid hormone secretion: 1) impaired renal function causes decreased excretion of phosphate and elevation of serum phosphate, which depresses serum calcium and thereby stimulates parathyroid hormone secretion, 16 2) renal failure produces resistance to vitamin D, which decreases intestinal absorption of calcium and causes further parathyroid hormone stimulation, 17 and 3) uremia inhibits the calcemic action of parathyroid hormone and, thus, greater production of the hormone is required to achieve an equivalent metabolic effect. 18 Serum calcium levels in secondary hyperparathyroidism usually are normal or low. Precipitation of calcium phosphate crystals in the arteries, subcutaneous tissues and viscera occurs when the serum calcium-phosphate product exceeds plasma solubility, which varies from 60 to 75 mg./dl., depending upon normal laboratory values. 19·20 The fact that arterial calcifications seldom resolve and may progress despite successful renal transplantation 11 • 21 has been attributed to the phenomenon of calciphylaxis. 22 Tissues that are sensitized during the uremic period by a systemic calcifying factor (parathyroid hormone, vitamin D or hypercalcemia) may calcify after subsequent exposure to a challenging agent. Serum calcium levels need not be elevated for challenging agents to cause calcium deposition in the already sensitized tissues. In the post-transplant period corticosteroid therapy, persistent hyperparathyroidism, hypercalcemia or vitamin D therapy may be the challenging factors that cause progressive calcification despite restoration of normal renal function. Distinct radiographic changes are found in patients with end stage renal disease and secondary hyperparathyroidism. Diffuse vascular and soft tissue calcifications usually are most pronounced in the small arteries and arterioles of the skin, subcutaneous tissue, and muscle of the hands and feet. 23 The most common skeletal changes are subperiosteal resorption, particularly of the hand and distal clavicles, and periosteal new bone formation (osteitis fibrosa). 23 The histological appearance of the arteries demonstrates marked luminal compression owing to calcific infiltration of the media, reactive connective tissue swelling and hyperplasia
of the intima. 10• 24 In contrast, diabetic small vessel disease results from atheromatous replacement of the intima, which eventually causes total obstruction. Although our patient had long-standing diabetes mellitus, histologically the arteries resembled the pattern associated with secondary hyperparathyroidism (fig. 2). Prevention of soft tissue and vascular calcification depends upon early aggressive medical management of secondary hyperparathyroidism.25 The re-establishment of normal serum calcium and phosphate levels will suppress the hyperactive parathyroid glands. This effect is achieved by use of elemental calcium and vitamin D analogue supplements, and by dialysis with a low phosphate and high calcium bath solution. 25 Most importantly, early aggressive therapy with oral phosphate binders to decrease gastrointestinal absorption of phosphate is indicated to prevent hyperphosphatemia and to maintain the serum calcium-phosphate product below its precipitation level. Despite these measures medical therapy may be ineffective in controlling the disease. Our patient, who received appropriate early medical intervention with oral phosphate binders, still had an elevated serum calcium-phosphate product (76.5 mg./ dl.) and progressive arterial calcification developed. Although the efficacy of subtotal parathyroidectomy remains controversial, 24 an operation is recommended for those uremic and transplant patients in whom progressive soft tissue and vascular calcifications develop despite medical therapy.11· 21 ·26, 27 Subtotal parathyroidectomy is most effective when performed before extensive necrosis, gangrene and sepsis develop. 11 Perloff and associates recommended subtotal parathyroidectomy for patients with extremity pain, elevated parathyroid hormone levels and extensive small vessel calcification radiographically even if they do not have obvious ischemic changes. 11 Subtotal parathyroidectomy frequently alleviates the vasculitic component and prevents further vascular deterioration, although it does not affect those vessels that already have calcified. 26 Gipstein and associates reported partial or complete healing of ischemic lesions in 70 per cent of their patients postoperatively.26 Our patient clearly benefited from subtotal parathyroidectomy as manifested by resolution of the digital cyanosis, prevention of progressive gangrene and healing of the penis. REFERENCES
1. Haddad, F. S.: Penile strangulation by human hair. Report of three cases and review of the literature. Urol. Int., 37: 375, 1982.
2. Khoriaty, N. and Schick, E.: Penile gangrene: an unusual complication of priapism. How to avoid it? Urology, 16: 280, 1980. 3. Fortuno, R. F. and Carrillo, R.: Gangrene of the penis following cavernospongiosum shunt in a case of priapism. J. Urol., 108: 752, 1972. 4. Rabinowitz, R. and Lewin, E. B.: Gangrene of the genitalia in children with Pseudomonas sepsis. J. Urol., 124: 431, 1980.
PENILE GANGREL\!E 5, 1-'ho:rnas, J. rf.: Fournier's gangrene of the penis and the scrotum, J. 75: 719, 1956. 6. Lowe, W. and Tassy, F.: Massive venous thrombosis and carcinoma of the lung. Amer. Rev. Resp. Dis., 95: 980, 1967. 7. S0dal, G., Ly, B. and Borchgrevink, H. H.: Thrombosis of the inferior vena cava, disseminated intravascular coagulation and gangrene of the penis. A case report. Acta Med. Scand., 203: 535, 1978. 8. Weinberg, A. C., Lieskovsky, G., McGehee, W. G. and Skinner, D. G.: Warfarin necrosis of the skin and subcutaneous tissue of the male external genitalia. J. Urol., 130: 352, 1983. 9. Vaughan, E. D., Moore, R. A., Warren, H., Moler, D. N. and Gillenwater, J. Y.: Skin necrosis of genitalia and warfarin therapy. J.A.M.A., 210: 2282, 1969. 10. Rosen, H., Friedman, S. A., Raizner, A. E. and Gerstmann, K.: Azotemic arteriopathy. Amer. Heart J., 84: 250, 1972. 11. Perloff, L. J., Spence, R. K., Grossman, R. A. and Barker, C. F.: Lethal post-transplantation calcinosis. Transplantation, 27: 21, 1979. 12. Kleeman, C. R., Massry, S. G., Coburn, J. W. and Popovtzer, M. M.: The problem and unanswered questions. Renal osteodystrophy, soft tissue calcification, and disturbed divalent ion metabolism in chronic renal failure. Arch. Intern. Med., 124: 262, 1969. 13. Parfitt, A. M.: Soft-tissue calcification in uremia. Arch. Intern. Med., 124: 544, 1969. 14. Pendras, J. P.: Parathyroid disease in long-term maintenance hemodialysis. Arch. Intern. Med., 124: 312, 1969. 15. Alfrey, A. C., Jenkins, D., Groth, C. G., Schorr, W. S., Gecelter, L. and Ogden, D. A.: Resolution of hyperparathyroidism, renal osteodystrophy and metastatic calcification after renal homotransplantation. New Engl. J. Med., 279: 1349, 1968. 16. Bricker, N. S.: On the pathogenesis of the uremic state. An exposition of the "trade-off hypothesis". New Engl. J. Med., 286: 1093, 1972. 17. DeLuca, H. F.: The kidney as an endocrine organ involved in
1191
cakiur.o homeost&siso Int., 4: 80, 1973. 18. Ivfassry, S. G., Coburn, Lee, D, B. N., JO'\iiJsey, J. and 'normone m . Kleeman, C. R.: Skeletal resistance to renal failure: studies in 105 human Intern. Med., 78: 1973. K., Miller, H. G. and Richardson, G. 0.: Chronic renal 19. Herbert, disease, secondary parathyroid hyperplasia, decakification of bone and metastatic calcification. J. Path. Bact., 53: 161, 1941. 20. Conn, J., Jr., Krumlovsky, F. A., Del Greco, F, and Sir,non, N. l\11.: Calciphylaxis: etiology of progressive vascular calcification and gangrene? Ann. Surg., 177: 206, 1973. 21. Ejerblad, S., Eriksson, I. and Wibell, L.: Arterial disease with ischemic ulcerations in renal transplanted recipients. Scand. J. Urol. NephroL, suppl. 42, p. 186, 1977. 22. Selye, H.: Calciphylaxis. Chicago: University of Chicago Press, 1962. 23. Peterson, R.: Small vessel calcification and its relationship to secondary hyperparathyroidism in the renal homotransplant patient. Radiology, 126: 627, 1978. 24. Chan, Y. L., Mahony, J. F., Turner, J. J. and Posen, S.: The vascular lesions associated with skin necrosis in renal disease. Brit. J. Derm., 109: 85, 1983. 25. Johnson, W. J., Goldsmith, R. S., Beabout, J. W., Jowsey, J., Kelly, P. J. and Arnaud, C. D.: Prevention and reversal of progressive secondary hyperparathyroidism in patients maintained by hemodialysis. Amer. J. Med., 56: 827, 1974. 26. Gipstein, R. M., Coburn, J. W., Adams, D. A., Lee, D. B. N., Parsa, KP., Sellers, A., Suki, W. N. and Massry, S. G.: Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure. Arch. Intern. Med., 136: 1273, 1976. 27. Massry, S. G., Gordon, A., Coburn, J. W., Kaplan, L., Franklin, S. S., Maxwell, M. H. and Kleeman, C. R.: Vascular calcification and peripheral necrosis in a renal c1a.u~µ1,,uc Reversal of lesions following subtotal yn}idlectoiny J. Med., 49: 416, 1970.
THE JOURNAL OF UROLOGY
Copyright© 1984 by The Williams & Wilkins Co.
Printed in U.S.A.
PENILE GANGRENE: A COMPLICATION OF SECONDARY HYPERPARATHYROIDISM FROM CHRONIC RENAL FAILURE FRANKLIN C. LOWE
AND
CHARLES B. BRENDLER
From the Department of Urology, The Johns Hopkins University School of Medicine, James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland
ABSTRACT
We present the third case and first reported survivor of penile gangrene due to secondary hyperparathyroidism from chronic renal failure. The patient was treated with distal penectomy and subtotal parathyroidectomy. This case stimulated us to review the metabolic and vascular changes associated with secondary hyperparathyroidism in chronic renal failure. Secondary hyperparathyroidism may cause diffuse vasculitis and vascular calcification, which can lead to widespread ischemic necrosis and gangrene. Early medical therapy, including oral phosphate binders, is crucial to maintain the serum calcium-phosphate product below precipitation level. Subtotal parathyroidectomy is indicated for patients in whom progressive arterial and soft tissue calcification develops despite medical therapy. Gangrene of the penis can result from a variety of causes, including tourniquet syndrome,1 priapism, 2 •3 infection, 4 •5 venous thrombosis, 6 • 7 warfarin therapy8 • 9 and azotemic secondary hyperparathyroidism. 10• 11 We present the third reported case and the first survivor with penile gangrene from azotemic secondary hyperparathyroidism. The remaining 2 patients died of overwhelming sepsis. This case provided the impetus to review the metabolic and vascular changes that result from secondary hyperparathyroidism due to chronic renal failure. Since urologists and transplant surgeons frequently treat patients with end stage renal disease it is important to be aware of these problems. CASE REPORT
W. S., a 60-year-old white man with adult onset insulindependent diabetes mellitus and chronic renal failure, presented with dry gangrene of the penis in December 1983. The diabetes had been well controlled with 24 units of neutral protein Hagedorn insulin daily since 1960. The patient had renal insufficiency secondary to Kimmelstiel-Wilson disease, with a stable serum creatinine level of 4.0 mg./dl. until February 1981, when right radical nephrectomy was done for stage I renal cell carcinoma. Postoperatively, the serum creatinine increased to 8.0 mg./dl. and progressive renal failure ensued. Hemodialysis was begun in June 1983 via an arterial venous fistula in the left forearm. Painful cyanosis of the left fingers developed while the patient was on hemodialysis. This condition was attributed to arterial steal and peritoneal dialysis was started in November. Shortly thereafter the patient suffered dry gangrene of several fingers and toes. Two painful blisters arose on the glans penis that soon ulcerated. Biopsy of the penile ulcers revealed necrotic tissue only with no evidence of malignant, fungal or granulomatous disease. The 2 ulcers became progressively necrotic and within 4 weeks the entire glans was a dry gangrenous eschar. Initial management was conservative because of patient concern over the ability of a surgical incision to heal. However, penile pain became uncontrollable even with narcotics and the patient was referred to the urology service for evaluation. At that time the glans penis was a black, hard eschar with a pinpoint meatal opening (fig. 1). The proximal penile shaft was indurated but appeared viable. Doppler evaluation of the penis revealed no arterial pulsations. Shoddy bilateral inguinal adenopathy was noted. Other areas of dry gangrene included the Accepted for publication August 2, 1984.
left great toe, left index finger, left fifth finger and the right index finger. All 10 fingers were cyanotic. The right radial, right posterior tibialis, left dorsalis pedis and left posterior tibialis pulses were absent. Significant laboratory data included serum calcium 9.0 mg./ dl. (8.5 to 10.5 mg./dl.), phosphate 8.5 mg./dl. (2.5 to 4.5 mg./ dl.), alkaline phosphatase 240 mu./ml. (11 to 87 mu./ml.), parathyroid hormone levels intact 1,103 pg./ml. (7 to 330 pg./ ml.) and n-terminal 1,370 pg./ml. (230 to 630 pg./ml.). The serum calcium-phosphate product was 76.5 mg./dl. (60 to 75 mg./dl.). Radiographs of the extremities showed marked periosteal resorption as well as extensive calcification of the small and medium-sized vessels. Distal penectomy was performed to control the pain, and to prevent the development of progressive gangrene and cellulitis. During the procedure there was minimal bleeding from the skin, subcutaneous tissues and corpora cavernosa, both of which were thrombosed. The dorsal penile artery was calcified completely. Postoperatively, the patient immediately was rendered free of pain for the first time in 3 months. Five days after partial penectomy subtotal parathyroidectomy with removal of 3½ hyperplastic glands was performed with the hope of stabilizing the generalized vascular deterioration and to promote healing of the penile wound. Postoperatively, the digital cyanosis resolved promptly and the penis healed completely within 3 weeks. Serum calcium decreased to 5.6 mg./dl. but was stabilized with oral calcium and vitamin D supplements. Subsequently, the gangrenous left index and fifth fingers were amputated. A left below-the-knee amputation also was performed because of failure to heal an ankle and foot ulcer. Presently, the patient continues on peritoneal dialysis in stable condition without any new areas of gangrene. DISCUSSION
Manifestations of altered calcium metabolism occur com monly in patients with end stage renal disease. Renal osteodystrophy occurs early in about 25 per cent of the patients with chronic renal failure. As many as 80 per cent of the patients on long-term hemodialysis have soft tissue calcifications and bony abnormalities. 12 Soft tissue calcifications most commonly are arterial but ocular, periarticular, visceral and cutaneous involvement also occur. 13 Arterial calcification occurs in approximately 20 per cent of the patients in the early stages of chronic renal failure and up to 75 per cent of those with advanced secondary hyperparathyroidism. 14 Secondary hyperparathy-
1189
1190
LOWE AND BRENDLER
FIG. 2. Cross-sectional photomicrograph shows intraluminal calcifications (arrow) in dorsal penile artery. Reduced from X60. FIG. 1. Preoperative photograph demonstrates gangrenous glans penis with viable penile shaft.
roidism and its manifestations usually resolve after successful renal transplantation. 15 However, renal osteodystrophy, metastatic calcification and lethal calcinosis can occur after transplantation. 11 • 15 Arterial and metastatic soft tissue calcification in patients with uremia results from secondary hyperparathyroidism with high parathyroid hormone levels, hyperphosphatemia and connective tissue changes. 13 Three mechanisms are responsible for the increased parathyroid hormone secretion: 1) impaired renal function causes decreased excretion of phosphate and elevation of serum phosphate, which depresses serum calcium and thereby stimulates parathyroid hormone secretion, 16 2) renal failure produces resistance to vitamin D, which decreases intestinal absorption of calcium and causes further parathyroid hormone stimulation, 17 and 3) uremia inhibits the calcemic action of parathyroid hormone and, thus, greater production of the hormone is required to achieve an equivalent metabolic effect. 18 Serum calcium levels in secondary hyperparathyroidism usually are normal or low. Precipitation of calcium phosphate crystals in the arteries, subcutaneous tissues and viscera occurs when the serum calcium-phosphate product exceeds plasma solubility, which varies from 60 to 75 mg./dl., depending upon normal laboratory values. 19·20 The fact that arterial calcifications seldom resolve and may progress despite successful renal transplantation 11 • 21 has been attributed to the phenomenon of calciphylaxis. 22 Tissues that are sensitized during the uremic period by a systemic calcifying factor (parathyroid hormone, vitamin D or hypercalcemia) may calcify after subsequent exposure to a challenging agent. Serum calcium levels need not be elevated for challenging agents to cause calcium deposition in the already sensitized tissues. In the post-transplant period corticosteroid therapy, persistent hyperparathyroidism, hypercalcemia or vitamin D therapy may be the challenging factors that cause progressive calcification despite restoration of normal renal function. Distinct radiographic changes are found in patients with end stage renal disease and secondary hyperparathyroidism. Diffuse vascular and soft tissue calcifications usually are most pronounced in the small arteries and arterioles of the skin, subcutaneous tissue, and muscle of the hands and feet. 23 The most common skeletal changes are subperiosteal resorption, particularly of the hand and distal clavicles, and periosteal new bone formation (osteitis fibrosa). 23 The histological appearance of the arteries demonstrates marked luminal compression owing to calcific infiltration of the media, reactive connective tissue swelling and hyperplasia
of the intima. 10• 24 In contrast, diabetic small vessel disease results from atheromatous replacement of the intima, which eventually causes total obstruction. Although our patient had long-standing diabetes mellitus, histologically the arteries resembled the pattern associated with secondary hyperparathyroidism (fig. 2). Prevention of soft tissue and vascular calcification depends upon early aggressive medical management of secondary hyperparathyroidism.25 The re-establishment of normal serum calcium and phosphate levels will suppress the hyperactive parathyroid glands. This effect is achieved by use of elemental calcium and vitamin D analogue supplements, and by dialysis with a low phosphate and high calcium bath solution. 25 Most importantly, early aggressive therapy with oral phosphate binders to decrease gastrointestinal absorption of phosphate is indicated to prevent hyperphosphatemia and to maintain the serum calcium-phosphate product below its precipitation level. Despite these measures medical therapy may be ineffective in controlling the disease. Our patient, who received appropriate early medical intervention with oral phosphate binders, still had an elevated serum calcium-phosphate product (76.5 mg./ dl.) and progressive arterial calcification developed. Although the efficacy of subtotal parathyroidectomy remains controversial, 24 an operation is recommended for those uremic and transplant patients in whom progressive soft tissue and vascular calcifications develop despite medical therapy.11· 21 ·26, 27 Subtotal parathyroidectomy is most effective when performed before extensive necrosis, gangrene and sepsis develop. 11 Perloff and associates recommended subtotal parathyroidectomy for patients with extremity pain, elevated parathyroid hormone levels and extensive small vessel calcification radiographically even if they do not have obvious ischemic changes. 11 Subtotal parathyroidectomy frequently alleviates the vasculitic component and prevents further vascular deterioration, although it does not affect those vessels that already have calcified. 26 Gipstein and associates reported partial or complete healing of ischemic lesions in 70 per cent of their patients postoperatively.26 Our patient clearly benefited from subtotal parathyroidectomy as manifested by resolution of the digital cyanosis, prevention of progressive gangrene and healing of the penis. REFERENCES
1. Haddad, F. S.: Penile strangulation by human hair. Report of three cases and review of the literature. Urol. Int., 37: 375, 1982.
2. Khoriaty, N. and Schick, E.: Penile gangrene: an unusual complication of priapism. How to avoid it? Urology, 16: 280, 1980. 3. Fortuno, R. F. and Carrillo, R.: Gangrene of the penis following cavernospongiosum shunt in a case of priapism. J. Urol., 108: 752, 1972. 4. Rabinowitz, R. and Lewin, E. B.: Gangrene of the genitalia in children with Pseudomonas sepsis. J. Urol., 124: 431, 1980.
PENILE GANGREL\!E 5, 1-'ho:rnas, J. rf.: Fournier's gangrene of the penis and the scrotum, J. 75: 719, 1956. 6. Lowe, W. and Tassy, F.: Massive venous thrombosis and carcinoma of the lung. Amer. Rev. Resp. Dis., 95: 980, 1967. 7. S0dal, G., Ly, B. and Borchgrevink, H. H.: Thrombosis of the inferior vena cava, disseminated intravascular coagulation and gangrene of the penis. A case report. Acta Med. Scand., 203: 535, 1978. 8. Weinberg, A. C., Lieskovsky, G., McGehee, W. G. and Skinner, D. G.: Warfarin necrosis of the skin and subcutaneous tissue of the male external genitalia. J. Urol., 130: 352, 1983. 9. Vaughan, E. D., Moore, R. A., Warren, H., Moler, D. N. and Gillenwater, J. Y.: Skin necrosis of genitalia and warfarin therapy. J.A.M.A., 210: 2282, 1969. 10. Rosen, H., Friedman, S. A., Raizner, A. E. and Gerstmann, K.: Azotemic arteriopathy. Amer. Heart J., 84: 250, 1972. 11. Perloff, L. J., Spence, R. K., Grossman, R. A. and Barker, C. F.: Lethal post-transplantation calcinosis. Transplantation, 27: 21, 1979. 12. Kleeman, C. R., Massry, S. G., Coburn, J. W. and Popovtzer, M. M.: The problem and unanswered questions. Renal osteodystrophy, soft tissue calcification, and disturbed divalent ion metabolism in chronic renal failure. Arch. Intern. Med., 124: 262, 1969. 13. Parfitt, A. M.: Soft-tissue calcification in uremia. Arch. Intern. Med., 124: 544, 1969. 14. Pendras, J. P.: Parathyroid disease in long-term maintenance hemodialysis. Arch. Intern. Med., 124: 312, 1969. 15. Alfrey, A. C., Jenkins, D., Groth, C. G., Schorr, W. S., Gecelter, L. and Ogden, D. A.: Resolution of hyperparathyroidism, renal osteodystrophy and metastatic calcification after renal homotransplantation. New Engl. J. Med., 279: 1349, 1968. 16. Bricker, N. S.: On the pathogenesis of the uremic state. An exposition of the "trade-off hypothesis". New Engl. J. Med., 286: 1093, 1972. 17. DeLuca, H. F.: The kidney as an endocrine organ involved in
1191
cakiur.o homeost&siso Int., 4: 80, 1973. 18. Ivfassry, S. G., Coburn, Lee, D, B. N., JO'\iiJsey, J. and 'normone m . Kleeman, C. R.: Skeletal resistance to renal failure: studies in 105 human Intern. Med., 78: 1973. K., Miller, H. G. and Richardson, G. 0.: Chronic renal 19. Herbert, disease, secondary parathyroid hyperplasia, decakification of bone and metastatic calcification. J. Path. Bact., 53: 161, 1941. 20. Conn, J., Jr., Krumlovsky, F. A., Del Greco, F, and Sir,non, N. l\11.: Calciphylaxis: etiology of progressive vascular calcification and gangrene? Ann. Surg., 177: 206, 1973. 21. Ejerblad, S., Eriksson, I. and Wibell, L.: Arterial disease with ischemic ulcerations in renal transplanted recipients. Scand. J. Urol. NephroL, suppl. 42, p. 186, 1977. 22. Selye, H.: Calciphylaxis. Chicago: University of Chicago Press, 1962. 23. Peterson, R.: Small vessel calcification and its relationship to secondary hyperparathyroidism in the renal homotransplant patient. Radiology, 126: 627, 1978. 24. Chan, Y. L., Mahony, J. F., Turner, J. J. and Posen, S.: The vascular lesions associated with skin necrosis in renal disease. Brit. J. Derm., 109: 85, 1983. 25. Johnson, W. J., Goldsmith, R. S., Beabout, J. W., Jowsey, J., Kelly, P. J. and Arnaud, C. D.: Prevention and reversal of progressive secondary hyperparathyroidism in patients maintained by hemodialysis. Amer. J. Med., 56: 827, 1974. 26. Gipstein, R. M., Coburn, J. W., Adams, D. A., Lee, D. B. N., Parsa, KP., Sellers, A., Suki, W. N. and Massry, S. G.: Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure. Arch. Intern. Med., 136: 1273, 1976. 27. Massry, S. G., Gordon, A., Coburn, J. W., Kaplan, L., Franklin, S. S., Maxwell, M. H. and Kleeman, C. R.: Vascular calcification and peripheral necrosis in a renal c1a.u~µ1,,uc Reversal of lesions following subtotal yn}idlectoiny J. Med., 49: 416, 1970.