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Dehydroepiandrosterone replacement in addison’s disease
European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 96±97
Case report
Dehydroepiandrosterone replacement in addison's disease S. Samuel Kima,*, K. Heather Brodyb a
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98105, USA b Women's Health and Reproductive Center, Lakewood, CA, USA
Received 09 December 1999; received in revised form 20 August 2000; accepted 10 September 2000
Abstract Addison's disease is a rare endocrine disorder which can be life-threatening. It can also interfere with the normal development of adrenarche, resulting in the absence of pubic and axillary hair growth. We report a case of satisfactory restoration of adrenarche through DHEA administered in conjunction with the standard glucocortisone and ¯uorocortisone replacement. # 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Addison's disease; Adrenal insuf®ciency; DHEA replacement; Adrenarche
1. Introduction
2. Case report
Addison's disease is a rare endocrine disorder which can be life-threatening. About 70% of cases are due to idiopathic atrophy of the adrenal cortex, probably by autoimmune process. The principle hormones produced by the adrenal cortex are cortisol, aldosterone, and dehydroepiandrosterone (DHEA). Treatment of Addison's disease consists of replacement of the missing hormones, cortisol and aldosterone, which are crucial for survival in situations of major stress. The replacement of cortisol and aldosterone has been well established as the standard treatment for Addison's disease. However, DHEA replacement has been neglected due to the unknown role of this steroid and the fact that it has no vital effect on survival. DHEA serves as a prehormone in hair follicles and undiagnosed or untreated Addison's disease can interfere profoundly with the normal development of sexual hair (adrenarche), even with the normal development of menarche. The lack of sexual hair growth can create a negative self-image for individuals going through puberty. We report a case of successful treatment of Addison's disease, and the satisfactory restoration of adrenarche through DHEA administered in conjunction with the standard glucocortisone and ¯uorocortisone replacement.
A 24-year-old, nulligravida female, who had experienced irregular menstruation since menarche at age 13, presented with the complaint of neither axillary nor pubic hair growth. The patient stated that since childhood she had experienced fatigue and shortness of breath with strenuous exercise. She also revealed a history of frequent upper respiratory infections and hospitalizations as a child. She had normal breast development (thelarche) followed by normal menarche. However, neither axillary nor pubic hair growth (adrenarche) was noted. Pelvic examination and sonogram revealed normal development of the internal and external genitalia, except for the lack of axillary and pubic hair growth (Tanner stage I). Breast examination revealed normal adult type symmetric breasts (Tanner stage V). It was also noticed that her skin pigmentation was darker than that of her family. Laboratory tests revealed decreased androgen (testosterone <10 ng/dl, normal range: 10±70 ng/dl; DHEAS 5 mg/dl, normal range: 65±380 mg/dl), decreased cortisol (2.3 mg/dl, normal range: 7.0±25.0 mg/dl), and increased ACTH (786 pg/ ml, normal range: 9±52 pg/ml). Fasting blood glucose was mildly decreased to 58 mg/dl (normal range: 65±115 mg/dl). Electrolytes (sodium 141 mEq/l; potassium 3.9 mEq/l) were within normal limits, and adrenal antibodies were negative. The laboratory results con®rmed a diagnosis of Addison's disease, the etiology of absence of axillary and pubic hair growth (no adrenarche). The patient was treated with hydrocortisone and ¯uorocortisone combined with DHEA replacement to promote sexual hair growth.
* Corresponding author. Tel.: 1-206-543-4693; fax: 1-206-685-7818. E-mail address: [email protected] (S.S. Kim).
0301-2115/01/$ ± see front matter # 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 1 - 2 1 1 5 ( 0 0 ) 0 0 5 0 0 - 5
S.S. Kim, K.H. Brody / European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 96±97
Optimal dosages of the steroid hormones including DHEA were adjusted with serial blood tests. After the treatment with daily dose of 50 mg DHEA for 6 months, the serum DHEAS and testosterone level elevated to 575.2 mg/dl and 63 ng/dl, respectively. Daily DHEA dosage was adjusted to 25 mg to minimize the potential adverse effects with long-term use. Serum DHEAS and testosterone levels were monitored every 3 month. Follow-up in 2 years revealed Tanner stage III pubic hair growth, sparse axillary hair growth, and decreased skin pigmentation. The patient also reported regulation of her menstrual cycles with ongoing treatment. DHEAS level was stabilized between 118±169 mg/dl with an adjusted dosage of DHEA. Testosterone level was also stabilized between 14±16 ng/dl. Currently she is on daily maintenance dosage of hydrocortisone (hydrocort) 40 mg, ¯uorocortisone (¯orinef) 0.1 mg, and DHEA 25 mg. 3. Discussion This case illustrates the potential role of DHEA in the treatment of Addison's disease, especially for the patient who cannot achieve adrenarche due to adrenal insuf®ciency. Dehydroepiandrosterone and dehydroepiandrosterone sulfate are 19-carbon steroids, secreted almost exclusively by the adrenal cortex (Zona reticularis) [1]. The mechanism of DHEA action remains unclear.DHEA exerts its chief physiologic activity after conversion to testosterone and dihydrotestosterone, which stimulates sexual hair growth. Although testosterone is more potent androgen, it would be more logical and safer to replace DHEA, the missing adrenal androgen in Addison's disease, which can be easily absorbed after oral ingestion and readily converted to androgen. It has been reported that DHEA improves well-being and sexuality in women with adrenal insuf®ciency and suggested
97
that DHEA become part of the hormone replacement regimen in women with adrenal insuf®ciency [2]. Although it is dif®cult to de®ne the optimum DHEA replacement dose, the pharmacokinetic studies indicated that the administration of 50 mg dose of DHEA restored plasma testosterone and DHEA levels in the range of those in young women [3,4]. Our case report suggested that daily dose of 25 mg DHEA can be used as a maintenance dose for a long-term replacement therapy in some individuals. Despite the accumulation of research, no long-term human studies have been performed demonstrating the safety of DHEA use over an extended period of time. Of particular concern in long-term use of excessive DHEA are the potential adverse effects to the liver, breast, and prostate. The role of DHEA replacement for the postmenopausal woman as well as the premenopausal woman in situations where endogenous adrenal androgen secretion is low, such as in hypopituitarism and in adrenal insuf®ciency, should undergo further investigation.
References [1] Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ. The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3b-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 1996;81:3558±65. [2] Arlt W, Callies F, Van Vlijmen et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 1999;341:1013±20. [3] Arlt W, Justl H, Callies F et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab 1998;83:1928± 34. [4] Young J, Couzinet B, Nahoul K et al. Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans. J Clin Endocrinol Metab 1997;82:2578±85.
Case report
Dehydroepiandrosterone replacement in addison's disease S. Samuel Kima,*, K. Heather Brodyb a
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98105, USA b Women's Health and Reproductive Center, Lakewood, CA, USA
Received 09 December 1999; received in revised form 20 August 2000; accepted 10 September 2000
Abstract Addison's disease is a rare endocrine disorder which can be life-threatening. It can also interfere with the normal development of adrenarche, resulting in the absence of pubic and axillary hair growth. We report a case of satisfactory restoration of adrenarche through DHEA administered in conjunction with the standard glucocortisone and ¯uorocortisone replacement. # 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Addison's disease; Adrenal insuf®ciency; DHEA replacement; Adrenarche
1. Introduction
2. Case report
Addison's disease is a rare endocrine disorder which can be life-threatening. About 70% of cases are due to idiopathic atrophy of the adrenal cortex, probably by autoimmune process. The principle hormones produced by the adrenal cortex are cortisol, aldosterone, and dehydroepiandrosterone (DHEA). Treatment of Addison's disease consists of replacement of the missing hormones, cortisol and aldosterone, which are crucial for survival in situations of major stress. The replacement of cortisol and aldosterone has been well established as the standard treatment for Addison's disease. However, DHEA replacement has been neglected due to the unknown role of this steroid and the fact that it has no vital effect on survival. DHEA serves as a prehormone in hair follicles and undiagnosed or untreated Addison's disease can interfere profoundly with the normal development of sexual hair (adrenarche), even with the normal development of menarche. The lack of sexual hair growth can create a negative self-image for individuals going through puberty. We report a case of successful treatment of Addison's disease, and the satisfactory restoration of adrenarche through DHEA administered in conjunction with the standard glucocortisone and ¯uorocortisone replacement.
A 24-year-old, nulligravida female, who had experienced irregular menstruation since menarche at age 13, presented with the complaint of neither axillary nor pubic hair growth. The patient stated that since childhood she had experienced fatigue and shortness of breath with strenuous exercise. She also revealed a history of frequent upper respiratory infections and hospitalizations as a child. She had normal breast development (thelarche) followed by normal menarche. However, neither axillary nor pubic hair growth (adrenarche) was noted. Pelvic examination and sonogram revealed normal development of the internal and external genitalia, except for the lack of axillary and pubic hair growth (Tanner stage I). Breast examination revealed normal adult type symmetric breasts (Tanner stage V). It was also noticed that her skin pigmentation was darker than that of her family. Laboratory tests revealed decreased androgen (testosterone <10 ng/dl, normal range: 10±70 ng/dl; DHEAS 5 mg/dl, normal range: 65±380 mg/dl), decreased cortisol (2.3 mg/dl, normal range: 7.0±25.0 mg/dl), and increased ACTH (786 pg/ ml, normal range: 9±52 pg/ml). Fasting blood glucose was mildly decreased to 58 mg/dl (normal range: 65±115 mg/dl). Electrolytes (sodium 141 mEq/l; potassium 3.9 mEq/l) were within normal limits, and adrenal antibodies were negative. The laboratory results con®rmed a diagnosis of Addison's disease, the etiology of absence of axillary and pubic hair growth (no adrenarche). The patient was treated with hydrocortisone and ¯uorocortisone combined with DHEA replacement to promote sexual hair growth.
* Corresponding author. Tel.: 1-206-543-4693; fax: 1-206-685-7818. E-mail address: [email protected] (S.S. Kim).
0301-2115/01/$ ± see front matter # 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 1 - 2 1 1 5 ( 0 0 ) 0 0 5 0 0 - 5
S.S. Kim, K.H. Brody / European Journal of Obstetrics & Gynecology and Reproductive Biology 97 (2001) 96±97
Optimal dosages of the steroid hormones including DHEA were adjusted with serial blood tests. After the treatment with daily dose of 50 mg DHEA for 6 months, the serum DHEAS and testosterone level elevated to 575.2 mg/dl and 63 ng/dl, respectively. Daily DHEA dosage was adjusted to 25 mg to minimize the potential adverse effects with long-term use. Serum DHEAS and testosterone levels were monitored every 3 month. Follow-up in 2 years revealed Tanner stage III pubic hair growth, sparse axillary hair growth, and decreased skin pigmentation. The patient also reported regulation of her menstrual cycles with ongoing treatment. DHEAS level was stabilized between 118±169 mg/dl with an adjusted dosage of DHEA. Testosterone level was also stabilized between 14±16 ng/dl. Currently she is on daily maintenance dosage of hydrocortisone (hydrocort) 40 mg, ¯uorocortisone (¯orinef) 0.1 mg, and DHEA 25 mg. 3. Discussion This case illustrates the potential role of DHEA in the treatment of Addison's disease, especially for the patient who cannot achieve adrenarche due to adrenal insuf®ciency. Dehydroepiandrosterone and dehydroepiandrosterone sulfate are 19-carbon steroids, secreted almost exclusively by the adrenal cortex (Zona reticularis) [1]. The mechanism of DHEA action remains unclear.DHEA exerts its chief physiologic activity after conversion to testosterone and dihydrotestosterone, which stimulates sexual hair growth. Although testosterone is more potent androgen, it would be more logical and safer to replace DHEA, the missing adrenal androgen in Addison's disease, which can be easily absorbed after oral ingestion and readily converted to androgen. It has been reported that DHEA improves well-being and sexuality in women with adrenal insuf®ciency and suggested
97
that DHEA become part of the hormone replacement regimen in women with adrenal insuf®ciency [2]. Although it is dif®cult to de®ne the optimum DHEA replacement dose, the pharmacokinetic studies indicated that the administration of 50 mg dose of DHEA restored plasma testosterone and DHEA levels in the range of those in young women [3,4]. Our case report suggested that daily dose of 25 mg DHEA can be used as a maintenance dose for a long-term replacement therapy in some individuals. Despite the accumulation of research, no long-term human studies have been performed demonstrating the safety of DHEA use over an extended period of time. Of particular concern in long-term use of excessive DHEA are the potential adverse effects to the liver, breast, and prostate. The role of DHEA replacement for the postmenopausal woman as well as the premenopausal woman in situations where endogenous adrenal androgen secretion is low, such as in hypopituitarism and in adrenal insuf®ciency, should undergo further investigation.
References [1] Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ. The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3b-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 1996;81:3558±65. [2] Arlt W, Callies F, Van Vlijmen et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 1999;341:1013±20. [3] Arlt W, Justl H, Callies F et al. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab 1998;83:1928± 34. [4] Young J, Couzinet B, Nahoul K et al. Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans. J Clin Endocrinol Metab 1997;82:2578±85.