J. Endocrinol. Invest. 13: 849-853, 1990
CASE REPORT
Hypogonadotropic hypogonadism in idiopathic hemochromatosis: evidence tor combined hypothalamic and pituitary involvement K. Siminoski*, M. D'Costa**, and P.G. Walfish* Departments of *Medicine and **Clinical Biochemistry, Mount Sinai Hospital and Medical School, University of Toronto, Toronto, Canada.
ABSTRACT. Hypogonadism is a common finding in idiopathic hemochromatosis. Most studies have localized the defect to either the pituitary gland or the testes. We describe a casewith evidence that favors the likely concomitant involvement of the hypothalamus as a factor in the observed hypogonadism. A clinically hypogonadal male with hemochromatosis had a low testosterorte concentration with inappropriately normal serum LH levels. Leydig cell function was intact, as demonstrated by anormal increase in serum testosterone
following HCG administration. However, although the pituitary secretion of LH was normal in response to GnRH stimulation, clomiphene administration did not produce an increase in LH and FSH, suggesting that there was a defect in the hypothalamic GnRH response. Since the FSH and prolactin responses to stimulatory testing were inadequate, coexisting pituitary dysfunction was likely also present. We conclude that this man had hypogonadism with laboratory evidence for a combined defect in hypothalamic and pituitary function.
INTRODUCTION Hypogonadism is common in men with hemochromatosis (1 -6). Most studies have found defects in either testicular or pituitary function, with little direct evidence of hypothalamic dysfunction as the source of hypogonadism. We describe a case of a hypogonadal male with hemochromatosis in whom hormonal testing suggested not only a defect in pituitary function but also a defect in hypothalamic gonadotropin regulation.
pation. Weight was stable, with no nausea, vomiting, or orthostatic complaints. There was no polyuria, polydipsia, or thirst. He reported that he had "always tanned weil". He shaved daily, but libido was decreased and he had beenimpotent for many years. Medication included acetylsalicylic acid for pain relief and glyburide 5 mg twice daily which maintained adequate glycemic control. Hemochromatosis had been diagnosed at age 37 following a liver biopsy that showed early portal cirrhosis and fibrosis with extensive Prussian Blue staining for iron. Phlebotomy had initially been carried out regularly for 2.5 years, but had been discontinued by the patient. Bilateral hip pain had occurred with destructive articular changes requiring surgical replacement of the left hip at age 42 and the right hip at age 45. At age 57, diabetes mellitus had been diagnosed, after the development of poIyuria and polydipsia, for which glyburide therapy had been initiated. There was no history of alcohol abuse, cardiac disease, or liver failure. There was no known family history of hemochromatosis or diabetes. He had two children who were weil, with normal iron indices. On examination, vital signs were normal with no
CASE REPORT A 62 year old man with hemochromatosis and diabetes mellitus presented with an 18 month history of pain secondary to loose bilateral total hip prostheses. There were no complaints of fatigue, temperature intolerance, hair or skin changes, or consti-
Key-words: Hemochromatosis, hypogonadism, hypothalamic and pituitary, clomiphene and GnRHtesting. Correspondence: Dr. P.G. Walfish, Division of Endocrinology, Room 781, Mount Sinai Hospital, 600 UniversityAvenue, Toronto, Ontario M5G 1X5, Canada.
Received January 23, 1990; accepted September3, 1990.
849
K. Siminoski, M. D'Coste and P.G. Walfish
Table 1 - TRH and GnRH Stimulation testing 1 Time (min)
0
20
30
45
Glucose (mmol/I) 13.2
10.2
8.8
7.5
6.7
TSH (mIU/I)
3.3
15.8
15.4
N0 2
11.8
LH (lU/I)
8.0
15.0
15.0
16.0
15.0
FSH (lU/I)
8.2
11.5
11.5
12.3
12.0
21.0
34.0
30.0
30.0
25.0
Prolactin (JLg/l)
terone, HCG was administered 4,000 units intramuscularly daily for 3 days. Prior to administration, serum testosterone was 0.4 nrnol/l, and it rose to 25 nmol/l on the third day of injections. Since the testes were able to produce testosterone, and since LH was inappropriately normal for the low testosterone level, pituitary and I or hypothalamic insufficiency were suggested. To assess pituitary function, TRH (200 J,Lg), GnRH (100 J,Lg) and insulin (0.15 U I kg) were administered (Table 1). Adequate hypoglycemia was not obtained, so insulin hypoglycemia was repeated using a larger dose of insulin (0.25 U Ikg) (Table 2). In response to stimulation, TSH rose from 3.2 to 15.8 mlU/I (normal 2-5 fold increase), cortison from 375 to 820 nmol/l (normal greater than 2-fold increase), and growth hormone from 1.5 to 14 J,Lg/l (normal greater than 10 J,Lg/I). Baseline prolactin levels were just above normal range at 21 J,Lg/l (normal
CASE REPORT
Hypogonadotropic hypogonadism in idiopathic hemochromatosis: evidence tor combined hypothalamic and pituitary involvement K. Siminoski*, M. D'Costa**, and P.G. Walfish* Departments of *Medicine and **Clinical Biochemistry, Mount Sinai Hospital and Medical School, University of Toronto, Toronto, Canada.
ABSTRACT. Hypogonadism is a common finding in idiopathic hemochromatosis. Most studies have localized the defect to either the pituitary gland or the testes. We describe a casewith evidence that favors the likely concomitant involvement of the hypothalamus as a factor in the observed hypogonadism. A clinically hypogonadal male with hemochromatosis had a low testosterorte concentration with inappropriately normal serum LH levels. Leydig cell function was intact, as demonstrated by anormal increase in serum testosterone
following HCG administration. However, although the pituitary secretion of LH was normal in response to GnRH stimulation, clomiphene administration did not produce an increase in LH and FSH, suggesting that there was a defect in the hypothalamic GnRH response. Since the FSH and prolactin responses to stimulatory testing were inadequate, coexisting pituitary dysfunction was likely also present. We conclude that this man had hypogonadism with laboratory evidence for a combined defect in hypothalamic and pituitary function.
INTRODUCTION Hypogonadism is common in men with hemochromatosis (1 -6). Most studies have found defects in either testicular or pituitary function, with little direct evidence of hypothalamic dysfunction as the source of hypogonadism. We describe a case of a hypogonadal male with hemochromatosis in whom hormonal testing suggested not only a defect in pituitary function but also a defect in hypothalamic gonadotropin regulation.
pation. Weight was stable, with no nausea, vomiting, or orthostatic complaints. There was no polyuria, polydipsia, or thirst. He reported that he had "always tanned weil". He shaved daily, but libido was decreased and he had beenimpotent for many years. Medication included acetylsalicylic acid for pain relief and glyburide 5 mg twice daily which maintained adequate glycemic control. Hemochromatosis had been diagnosed at age 37 following a liver biopsy that showed early portal cirrhosis and fibrosis with extensive Prussian Blue staining for iron. Phlebotomy had initially been carried out regularly for 2.5 years, but had been discontinued by the patient. Bilateral hip pain had occurred with destructive articular changes requiring surgical replacement of the left hip at age 42 and the right hip at age 45. At age 57, diabetes mellitus had been diagnosed, after the development of poIyuria and polydipsia, for which glyburide therapy had been initiated. There was no history of alcohol abuse, cardiac disease, or liver failure. There was no known family history of hemochromatosis or diabetes. He had two children who were weil, with normal iron indices. On examination, vital signs were normal with no
CASE REPORT A 62 year old man with hemochromatosis and diabetes mellitus presented with an 18 month history of pain secondary to loose bilateral total hip prostheses. There were no complaints of fatigue, temperature intolerance, hair or skin changes, or consti-
Key-words: Hemochromatosis, hypogonadism, hypothalamic and pituitary, clomiphene and GnRHtesting. Correspondence: Dr. P.G. Walfish, Division of Endocrinology, Room 781, Mount Sinai Hospital, 600 UniversityAvenue, Toronto, Ontario M5G 1X5, Canada.
Received January 23, 1990; accepted September3, 1990.
849
K. Siminoski, M. D'Coste and P.G. Walfish
Table 1 - TRH and GnRH Stimulation testing 1 Time (min)
0
20
30
45
Glucose (mmol/I) 13.2
10.2
8.8
7.5
6.7
TSH (mIU/I)
3.3
15.8
15.4
N0 2
11.8
LH (lU/I)
8.0
15.0
15.0
16.0
15.0
FSH (lU/I)
8.2
11.5
11.5
12.3
12.0
21.0
34.0
30.0
30.0
25.0
Prolactin (JLg/l)
terone, HCG was administered 4,000 units intramuscularly daily for 3 days. Prior to administration, serum testosterone was 0.4 nrnol/l, and it rose to 25 nmol/l on the third day of injections. Since the testes were able to produce testosterone, and since LH was inappropriately normal for the low testosterone level, pituitary and I or hypothalamic insufficiency were suggested. To assess pituitary function, TRH (200 J,Lg), GnRH (100 J,Lg) and insulin (0.15 U I kg) were administered (Table 1). Adequate hypoglycemia was not obtained, so insulin hypoglycemia was repeated using a larger dose of insulin (0.25 U Ikg) (Table 2). In response to stimulation, TSH rose from 3.2 to 15.8 mlU/I (normal 2-5 fold increase), cortison from 375 to 820 nmol/l (normal greater than 2-fold increase), and growth hormone from 1.5 to 14 J,Lg/l (normal greater than 10 J,Lg/I). Baseline prolactin levels were just above normal range at 21 J,Lg/l (normal
