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Nephrologie 1983;4(2):69-74
[Anomalies of human gonadal function in periodic hemodialysis: role of the
etiology of kidney failure and the role of iron overload].
[Article in French]
Dueymes JM, Caron P, Pourrat JP, Louvet JP, Conte JJ
Levels of testosterone, free testosterone, oestrogen, LH, FSH,
prolactin were measured in 39 dialysed men. A LHRH stimulation test
was performed. This study was analysed in function of the underlying
renal disease, the duration of hemodialysis, and serum ferritin
levels. In chronic glomerulonephritis serum gonadotrophins
concentrations were significantly higher than in chronic interstitial
nephritis or polycystic disease. A correlation between prolactin and
ferritin was found, which may reflect the pituitary iron overload.
Free testosterone levels were significantly lower in patients with
gynecomastia (23-29 patients). In fact, the most direct relationship
that we found with gynecomastia in dialysed men was with the free
testosterone/oestrogen ratio.
PMID: 6877481, UI: 83271729
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JAMA 1980 Jul 25;244(4):343-5
Hemosiderosis in hemodialysis patients. An autopsy study of 50 cases.
Ali M, Fayemi AO, Rigolosi R, Frascino J, Marsden T, Malcolm D
The distribution of stainable iron stores was investigated in various
organs of 50 hemodialysis patients with chronic renal disease. Massive
iron deposits were found in the liver and spleen. Among 18 patients
with severe hepatosplenic siderosis, iron deposits were abundant in
the adrenal glands, lymph nodes, and lungs and were sparse in the
heart, kidneys, and pancreas. There was an absence or scarcity of
stainable iron in bone marrow of 19 pats. In five of these
marrow-iron-depleted patients, serum concentrations of ferritin were
high. In long-term hemodialysis patients, a variety of factors make
massive iron overloads of various organs a likely occurrence, severe
hepatosplenic siderosis may occur in marrow-iron-depleted patients,
and serum ferritin levels in this setting may not always accurately
reflect the status of marrow iron store.
PMID: 7392125, UI: 80230133
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Clin Investig 1992 Jul;70(7):566-72
Testosterone treatment of men with idiopathic hemochromatosis.
Kley HK, Stremmel W, Kley JB, Schlaghecke R
Stadtisches Krankenhaus, Singen/Hohentwiel,
Heinrich-Heine-Universitat, Dusseldorf.
Patients with chronic liver disease usually exhibit low plasma levels
of testosterone with loss of libido and potency; this is also valid in
male patients suffering from idiopathic hemochromatosis (IHC), in whom
nowadays the diagnosis is made at an earlier age. Therefore, the
effect of testosterone treatment was studied in 10 patients with IHC.
After the application of 250 mg testosterone enanthate i.m., the
plasma testosterone (from 2.4 +/- 1.9 to 20.1 +/- 7.4 ng/ml) and
estradiol (from 17.4 +/- 6.3 to 38.5 +/- 14.2 pg/ml) levels increased
significantly. The rise of estradiol was in the range of controls and
smaller than reported in other chronic liver diseases. In a long-term
study, 250 mg testosterone enanthate was given 4-weekly for 33-96
months to 5 patients with IHC. General well-being, libido, and potency
recovered almost immediately. Over a treatment period of 27.3 patient
years, symptoms of hyperestrogenism (gynecomastia) or (portal vein)
thrombosis were not seen, both of which had been described in patients
with alcoholic liver cirrhosis. There was no deterioration of liver
function. The effect of testosterone treatment on the patients'
well-being and plasma hormone concentrations remained unchanged over
the whole period of testosterone treatment. Thus, in male patients
with IHC and lowered plasma testosterone, treatment with testosterone
enanthate may be instituted. Because of the positive effects on
general well-being, liver regeneration capacity, and potency,
testosterone should especially be administered to younger subjects
suffering from IHC.
PMID: 1392425, UI: 93005397
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Subject: thyroid/iron
Arch Intern Med 143 (10): 1890-1893 (Oct 1983)
Thyroid disease in hemochromatosis. Increased incidence in homozygous men.
Edwards CQ, Kelly TM, Ellwein G, Kushner JP
The thyroid function of 49 patients homozygous for the hemochromatosis
allele was studied by measurement of serum thyroxine and thyrotropin
concentrations. Of 34 homozygous men, three were found to be
hypothyroid (thyroxine, less than 3.0 micrograms/dL and thyrotropin,
greater than 40 ImU/mL) and one was hyperthyroid (thyroxine, 24
micrograms/dL). All 15 homozygous women had normal thyroid function.
The hypothyroid patients had elevated titers of antithyroid
antibodies. Histologic examination of the thyroid at autopsy of one
hypothyroid patient showed notable iron accumulation and fibrosis with
modest lymphocytic infiltration. The causative importance of iron
deposition in thyroid diseases associated with hemochromatosis was
suggested by the reversal of the usual sex ratio of thyroid
dysfunction. Men with hemochromatosis had a much greater iron load
than women, and they also had a surprisingly higher incidence of
thyroid disease. Iron may have caused injury to the thyroid, followed
by the development of antithyroid antibodies and hypothyroidism. The
frequency of thyroid disorders in men with hemochromatosis is about 80
times that of men in the general population.
Subject: Hypothyroid/coffee
COFFEE: fYI Found a case-control study showing coffee to protect against
thyroid
disease. They found a strong negative association (p<0.05) in 125 patients
with
thyroid disease and matched controls--the more coffee, the less thyroid
disease. After
adjustment for possible confounders, the association remained. They
postulate a
stimulatory effect of caffeine on the intracellular cyclic AMP production,
which
inhibits cell growth. (Linos et al., Does coffee consumption protect
against thyroid
disease? Acta Chir Scand 1989 Jun; 155(607) 317-320.)
Subject: thyroid
Eur J Haematol 1997 Aug;59(2):76-81
Incidence of endocrine complications and clinical disease severity related to
genotype analysis and iron overload in patients with beta-thalassaemia.
Jensen CE, Tuck SM, Old J, Morris RW, Yardumian A, De Sanctis V, Hoffbrand
AV, Wonke B
Department of Obstetrics and Gynaecology, The Whittington Hospital,
London, UK.
The incidence of endocrine dysfunction in relation to the detailed
genotype of beta-thalassaemia is investigated in this study. In
addition, the association of genotype to specific clinical features of
beta-thalassaemia is examined, together with the relationship between
serum ferritin levels and endocrine complications. Ninety-seven
patients were included, all with transfusion dependent
beta-thalassaemia. Patients were divided into 2 categories; group 1
consisted of patients with a beta0/beta0 genotype with or without a
concomitant alpha-globin gene deletion as well as patients with
beta0/beta+ or beta+/beta+ genotype and normal alpha-globin chain
synthesis. Group 2 included patients with beta+/beta+ or beta+/beta0
genotype and one alpha-globin chain deletion and those with a moderate
amount of beta-globin chain synthesis (beta++) and normal alpha-globin
chain synthesis. The results showed that group 1 patients were more
likely to have severe clinical disease (p=0.005). Sixty-four patients
(66%) had at least 1 endocrine disorder and 39 (40%) had multiple
endocrinopathies; the most common abnormality was hypogonadotrophic
hypogonadism (HH). There was a significant association between
patients with group 1 genotypes and the presence of HH and impaired
glucose tolerance or diabetes. A positive correlation was demonstrated
between serum ferritin concentrations and the presence of thyroid or
parathyroid dysfunction.
PMID: 9293854, UI: 97438079
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(HOME) Subject: hormone/osteo/iron/arthritis
Arthritis Rheum 1999 Apr;42(4):799-806
Elevated parathyroid hormone 44-68 and osteoarticular changes in patients with
genetic hemochromatosis.
Pawlotsky Y, Le Dantec P, Moirand R, Guggenbuhl P, Jouanolle AM, Catheline
M, Meadeb J, Brissot P, Deugnier Y, Chales G
Centre Hospitalier et Universitaire, Rennes, France.
OBJECTIVE: To determine whether the osteoarticular changes associated
with genetic hemochromatosis could be explained by metabolic
parathyroid hormone (PTH) disorders. METHODS: The study involved 210
patients with liver iron overload syndromes. Osteoarticular changes
were numerically scored as the number of damaged joints. PTH 1-84 and
44-68 were assayed. RESULTS: An increase in serum PTH 44-68 levels was
found in one-third of untreated patients who had no calcium or PTH
1-84 abnormalities. Serum PTH 44-68 levels correlated positively with
serum ferritin levels. In multivariate analyses, the number of
affected joints correlated positively with age, serum PTH 44-68
levels, and serum ferritin levels. CONCLUSION: Liver iron overload
syndromes, especially genetic hemochromatosis, are associated with
elevated circulating levels of PTH fragments containing the 44-68
region, which appears to play a role in osteoarticular changes. This
increase seems to be a consequence of iron overload.
PMID: 10211896, UI: 99226878
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Subject: thalassemia/iodine
Eur J Endocrinol 2000 Sep;143(3):319-25
Increased sensitivity to the inhibitory effect of excess iodide on thyroid
function in patients with beta-thalassemia major and iron overload and the
subsequent development of hypothyroidism.
Alexandrides T, Georgopoulos N, Yarmenitis S, Vagenakis AG
Endocrine Division, Department of Medicine, University of Patras
Medical School, Patras, Greece.
[Record supplied by publisher]
OBJECTIVE: Patients with beta-thalassemia frequently develop primary
hypothyroidism and other endocrine disorders due to iron overload. We
studied whether administration of excess iodide to patients with
apparently normal thyroid function could uncover an underlying thyroid
disease. DESIGN AND METHODS: Twenty-five patients, 10 prepubertal
(mean age 11+/-3 years) and 15 adults (mean age 23+/-5 years) with
normal thyroid hormone and TSH levels, a normal response of TSH to TRH
and negative thyroid peroxidase antibodies received 20mg iodide three
times daily for three weeks, and thyroid hormone and TSH levels were
measured weekly during, and for three weeks after, iodide
administration and every 3 months thereafter for the next 5 years.
RESULTS: During iodide administration there was a significant decrease
in thyroid hormone concentrations which remained within normal levels,
and a significant increase in TSH concentrations which in 14 out of 25
(56%) patients reached the hypothyroid level. Baseline TSH values were
higher in those patients who developed subclinical hypothyroidism
(2.31+/-0.71mU/l vs 1. 34+/-0.64mU/l, P=0.0016). Subclinical
hypothyroidism developed in 70% of prepubertal and in 47% of adult
patients. Serum ferritin was elevated in all patients. Nine of the
fourteen patients (64.3%) who developed subclinical hypothyroidism
during iodide administration developed hypothyroidism during the
5-year follow-up compared with only one of the eleven patients with a
normal response to iodide (P=0.004). CONCLUSIONS: Patients with
beta-thalassemia should not be exposed to excess iodide due to
increased sensitivity to its inhibitory effects on thyroid function.
The susceptible individuals frequently develop permanent
hypothyroidism in the following years.
Publication Types:
* Clinical trial
PMID: 11022172, UI: 20478148
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Subject: thyroid/radiology/MRI
AJR Am J Roentgenol 2000 Dec;175(6):1567-9
T2 relaxation rate as an index of pituitary iron overload in patients with
beta-thalassemia major.
Argyropoulou MI, Metafratzi Z, Kiortsis DN, Bitsis S, Tsatsoulis A,
Efremidis S
Department of Radiology, School of Medicine, University of Ioannina,
45110, Ioannina, Greece.
OBJECTIVE: In transfusion-dependent ss-thalassemia major, increased
iron deposition in the pituitary gland has a cytotoxic effect, leading
mainly to hypogonadotropic hypogonadism. Early detection and
quantification of iron in the pituitary gland are of particular
importance for successful treatment. The purpose of this study was to
evaluate the T2 relaxation rate (1/T2) as a marker of pituitary
siderosis. SUBJECTS AND METHODS: In 29 patients with ss-thalassemia
major and 40 controls, we assessed the 1/T2 of the pituitary gland in
a 1.5-T MR unit, using a multiecho spin-echo sequence. In all
patients, an extensive endocrine evaluation was performed, including
measurements of spontaneous and stimulated levels of gonadotropins,
thyroid hormones, growth hormone, insulinlike growth factor, and
adrenal hormones. RESULTS: A positive correlation was found between
the 1/T2 and the serum ferritin level (r = 0.73, p < 0.001). The 1/T2
was higher in patients (mean, 0.020 msec(-1); SD, 0.006) compared with
that of controls (mean, 0.011 msec(-1); SD, 0.001; p < 0.001). The
1/T2 was higher in patients with hypogonadotropic hypogonadism (mean,
0.024 msec(-1); SD, 0.006) in comparison with that of patients without
any pituitary dysfunction (mean, 0.017 msec(-1); SD, 0.004; p < 0.05).
CONCLUSION: The T2 relaxation rate could be used as an index of
pituitary iron overload, and it might be of value to monitor treatment
with deferoxamine in patients with ss-thalassemia major.
PMID: 11090376, UI: 20544695
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Subject: thyroid/early/children
J Pediatr Endocrinol Metab 2000 Jun;13(6):651-6
Early onset of endocrine abnormalities in beta-thalassemia major in a
developing country.
Gulati R, Bhatia V, Agarwal SS
Department of Genetics, Sanjay Gandhi Postgraduate Institute of
Medical Sciences, Lucknow, India.
Endocrine complications in patients with thalassemia major in
developing countries may be frequent due to suboptimal iron chelation.
Data from developing countries are scant. We prospectively evaluated
growth, growth hormone (GH), insulin-like growth factor I, thyroid
hormone, cortisol and glucose tolerance in 84 patients over one year.
Height standard deviation (SD) score of patients > 8 years (-2.2 +/-
1.5 against National Center for Health Statistics references) was
significantly lower than that of normal controls (-1.0 +/- 0.7, p <
0.001). 51% of patients had GH deficiency, 13% hypocortisolism and
7.9% diabetes/impaired glucose tolerance. Ten of 11 adolescents/young
adults had hypogonadism. Of 54 preadolescent children who underwent
dynamic testing, 18 (33%) had at least one endocrine deficiency other
than short stature. We conclude that hypogonadism and hypocortisolism
form important causes for morbidity in our thalassemic children.
Thalassemic patients in developing countries may be at risk for
endocrine deficiencies at younger ages.
PMID: 10905390, UI: 20361325
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Subject: Blackfan/thyroid
J Pediatr Endocrinol Metab 2000 Mar;13(3):325-8
Multiple endocrine abnormalities in a child with Blackfan-Diamond anemia and
hemochromatosis. Significant improvement of growth velocity and predicted adult
height following growth hormone treatment despite liver damage.
Lanes R, Muller A, Palacios A
Pediatric Endocrine Unit, Hospital de Clinicas Caracas, Erythrocyte
and Leucocyte Laboratory, Centro de Quimioterapia, Oncologia y
Hematologia and Clinica Avila, Caracas Venezuela.
We evaluated a short, prepubertal 13.9 year-old boy with
Blackfan-Diamond anemia and significant liver iron stores due to
multiple blood transfusions and found him to have several endocrine
abnormalities, including hypothyroidism, hypoparathyroidism, primary
and secondary hypogonadism and IGF-I insufficiency. Growth velocity
was poor despite treatment with levothyroxine, calcitriol, calcium and
aggressive therapy with chelating agents. After 25 months of treatment
with rhGH his growth velocity, height for age and PAH increased
significantly, suggesting a degree of sensitivity to GH despite his
liver damage.
PMID: 10714760, UI: 20177242
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Subject: thyroid
Acta Clin Belg 1999 Dec;54(6):334-45
[Endocrine complications of genetic hemochromatosis].
[Article in French]
Paris I, Hermans M, Buysschaert M
Service d'Endocrinologie et Nutrition, Cliniques Universitaires St
Luc, Bruxelles, Belgique.
The authors report the prevalence and severity of endocrine
complications in a cohort of 115 patients suffering form genetic
hemochromatosis and followed since two decades. Already 40% of them
had developed diabetes at the time of diagnosis of hemochromatosis,
which was made at the age of 50 +/- 12 years (m +/- SD). Hypogonadism
was evidenced in 42% of the patients. In most of them, it was
considered as secondary to pituitary lesions as assessed by GnRH
tests. No other endocrine complications, in particular thyroid
disease, were evidenced during follow up. On the other hand, it was
also of interest to note that liver cirrhosis was observed in 52% of
the patients at the time of hemochromatosis diagnosis. A relationship
between cirrhosis, diabetes and hypogonadism was also assessed in
these patients. We conclude to the still high prevalence of endocrine
complications in genetic hemochromatosis.
PMID: 10686706, UI: 20151322
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Subject: thyroid/aplastic anemia
Acta Paediatr Jpn 1995 Aug;37(4):534-6
Hypothyroidism and hypoparathyroidism in an 11 year old boy with
hemochromatosis secondary to aplastic anemia.
Himoto Y, Kanzaki S, Nomura H, Araki T, Takahashi Y, Seino Y
Department of Pediatrics, Fukuyama Municipal Hospital, Japan.
This is the first reported case, to our knowledge, of
hypoparathyroidism and hypothyroidism due to secondary hemochromatosis
with onset during childhood. The patient was a boy with refractory
aplastic anemia in whom primary hypothyroidism and hypoparathyroidism
became apparent at the age of 10 and 11 years old, respectively. He
had received a total of 100 L of transfused blood by the age of 10
years. The patient showed poor annual height gain due to primary
hypothyroidism, together with hypocalcemia, cataract and intracranial
calcification due to hypoparathyroidism. The early appearance of both
thyroid and parathyroid dysfunction in this patient may have been due
to the delay of initiation of iron-chelating agents and liver
dysfunction due to hepatitis type C.
PMID: 7572161, UI: 96054163
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Subject: thyroid/idiopathic/child
Hepatology 1981 Jan-Feb;1(1):58-64
Idiopathic neonatal iron storage involving the liver, pancreas, heart, and
endocrine and exocrine glands.
Goldfischer S, Grotsky HW, Chang CH, Berman EL, Richert RR, Karmarkar SD,
Roskamp JO, Morecki R
Autopsy studies of two infants, one a newborn, the other 4 months old,
revealed massive amounts of iron in lysosomes of hepatocytes and
pancreatic acinar cells. Iron, which had been transported across the
placenta, accumulated in the same cell types as in adults with primary
and secondary hemochromatosis. Hemosiderin was found in cardiac muscle
cells, gastric and intestinal glands, and endocrine and exocrine
organs including pituitary, thyroid, adrenals, islets of Langerhans,
and sublingual and sweat glands. The liver was the most affected organ
and the normal hepatic architecture was replaced by hepatocytes which
were arranged in cluster, pseudoacinar structures, and multinucleated
giant cells embedded in a collagen matrix. The islets of Langerhans
were hyperplastic and hypertrophic. Ten similar cases, in five
families, have been described; no patients liver longer than 4 months.
Neonatal iron storage disease is clinically and pathologically
distinct from Zellweger's cerebrohepatorenal syndrome and
hypermethioninemia (tyrosinemia) neonatal diseases in which large
stores of iron are present in hepatocytes. No abnormalities in serum
iron, ferritin, or transferrin concentrations were detected in five
parents of the affected children.
PMID: 7286889, UI: 82029068
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Subject: thyroid/hemodialysis
Clin Nephrol 1992 Aug;38(2):105-9
Primary hypothyroidism and multiple endocrine failure in association with
hemochromatosis in a long-term hemodialysis patient.
Shirota T, Shinoda T, Aizawa T, Mizukami T, Katakura M, Takasu N, Yamada T
Department of Geriatrics, Endocrinology and Metabolism, Shinshu
University School of Medicine, Matsumoto, Japan.
A 56-year-old male patient on chronic hemodialysis developed liver
cirrhosis. He received a total of 20 liters of blood transfusion.
Bronze pigmentation of the skin and iron deposition to the liver,
spleen, pancreas and thyroid gland, which was demonstrated by computed
tomography and magnetic resonance imaging studies, and histological
demonstration of iron deposition to the thyroid gland, bone marrow and
gastric mucosa established a diagnosis of secondary hemochromatosis.
Endocrine work-up revealed the presence of diabetes mellitus with
minimum insulin secretory response, primary (or thyroprivic)
hypothyroidism, hypoparathyroidism and hypogonadotropic hypogonadism.
A wide-spread endocrine involvement as seen in this patient is a rare
clinical feature of hemochromatosis secondary to massive blood
transfusion in hemodialysis patients. Particularly, primary
hypothyroidism due to iron deposition to the thyroid gland was quite a
rare feature of hemochromatosis.
PMID: 1516278, UI: 92386797
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Subject: thyroid/ferrous sulfate
South Med J 1997 Jun;90(6):637-9
Ferrous sulfate-induced increase in requirement for thyroxine in a patient with
primary hypothyroidism.
Shakir KM, Chute JP, Aprill BS, Lazarus AA
Department of Internal Medicine, National Naval Medical Center,
Bethesda, MD 20889-5600, USA.
Recent studies have shown that under experimental conditions ferrous
sulfate may reduce the gastrointestinal absorption of orally
administered levothyroxine sodium in patients with primary
hypothyroidism. We describe a patient who became hypothyroid while
taking ferrous sulfate. The hypothyroid status was corrected by
increasing the dose of levothyroxine. Subsequently, when ferrous
sulfate was discontinued, the patient became hyperthyroid while taking
the higher dose of thyroid hormone preparation. Since both
hypothyroidism and iron deficiency anemia may coexist, additional
thyroid function testing is recommended in patients treated
concurrently with ferrous sulfate and L-thyroxine.
PMID: 9191742, UI: 97335076
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Subject: thyroid/pruritus
Schweiz Med Wochenschr 1995 Nov 18;125(46):2244-50
[Pruritus--also a challenge in internal medicine].
[Article in German]
Brunner W
Medizinische Klinik, Kantonsspital Chur.
Generalized or localized itch without primary skin manifestations may
be the presenting symptom of serious internal diseases. Five
characteristic cases of pruritus are discussed: Hodgkin's disease,
primary sclerosing cholangitis, polycythemia vera, iron deficiency
(with pica), and uremia. Other important causes must be considered;
all forms of cholestasis, including primary biliary cirrhosis,
drug-induced, pregnancy-related, and extrahepatic cholestasis; other
hematologic and malignant disorders such as non-Hodgkin's lymphoma,
leukemia, multiple myeloma, solid tumors, and myelodysplastic
syndromes; metabolic and endocrine diseases, most notably diabetes
mellitus, hyperthyroidism, hypothyroidism, and carcinoid syndrome;
focal neurologic diseases such as brain tumors, cerebral infarctions
and multiple sclerosis; adverse drug reactions without rash;
infectious diseases, especially parasitic and HIV infections. A
diagnostic laboratory screening for pruritus of undetermined origin is
suggested.
PMID: 8525344, UI: 96091969
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Subject: ZINC/IRON/TESTOSTERONE
APPLIED NUTRITIONAL INVESTIGATION
Zinc Status and Serum Testosterone Levels of Healthy Adults
ANANDA S. PRASAD, MD, PHD, CHRIS S. MANTZOROS, MD, FRANCES W. J. BECK, PHD,
JOSEPH W. HESS, MD, AND GEORGE J. BREWER, MD
From the Department of Internal Medicine, Division of
Hematology-Oncolgoy, Wayne State University School of Medicine, Detroit,
Michigan, Departments of Human Genetics and Division of Endocrinology,
Department of Internal Medicine, Beth Israel Hospital, Harvard Medical
School, Boston, Massachusetts, USA
ABSTRACT
Zinc deficiency is prevalent throughout the world, including the USA.
Severe and moderate deficiency of zinc is associated with hypogonadism
in men. However, the effect of marginal zinc deficiency on serum
testosterone concentration is not known. We studied the relationship
between cellular zinc concentrations and serum testosterone
cross-sectionally in 40 normal men, 20 to 80 y of age. In four normal
young men (27.5±0.5 y), we measured serum testosterone before and
during marginal zinc deficiency induced by restricting dietary zinc
intake. We also measured serum testosterone in nine elderly men (64±9
y) who were marginally zinc deficient before and after 3 to 6 mo of
supplementation with 459 umol/ d oral zinc administered as zinc
gluconate. Serum testosterone concentrations were significantly
correlated with cellular zinc concentrations in the cross-sectional
study (lymphocyte zinc versus serum testosterone, r = 0.43, p = 0.006;
granulocyte zinc versus serum testosterone, r = 0.30, p = 0.03).
Dietary zinc restriction in normal young men was associated with a
significant decrease in serum testosterone concentrations after 20
weeks of zinc restriction (baseline versus post-zinc restriction
mean±SD, 39.9±7.1 versus 10.6±3.6 nmol/L, respectively; p = 0.005).
Zinc supplementation of marginally zinc-deficient normal elderly men
for six months resulted in an increase in serum testosterone from
8.3±6.3 to 16.0±4.4 nmol/L (p = 0.02). We conclude that zinc may play
an important role in modulating serum testosterone levels in normal
men. Nutrition 1996 12:344-348
Key words: zinc, serum testosterone, elderly
_________________________________________________________________
Subject: zinc/iron
Yip R, Reeves JD, Lonnerdal B, et al., "Does Iron Supplementation
Compromise Zinc Nutrition in Healthy Infants?", (Oct 1985), The
American Journal of Clinical Nutrition, 42 (4), pp: 683-7.
Subject: zinc/DNA/iron
_________________________________________________________________
J. Biol. Chem. 271: 5125-5130 (1996)[96214945]
In vivo and in vitro iron-replaced zinc finger generates free radicals and
causes DNA damage.
D. Conte, S. Narindrasorasak & B. Sarkar
Department of Biochemistry Research, The Hospital for Sick Children,
Toronto, Ontario M5G 1X8, Canada.
The estrogen receptor (ER) is a ligand-activated transcription factor
whose DNA-binding domain (ERDBD) has eight cysteines, which coordinate
two zinc atoms, forming two zinc finger-like structures. We
demonstrate the capability of iron to replace zinc in zinc finger
(hereby referred to as iron finger) both in vivo (using Escherichia
coli BL21 (DE3)) and in vitro. Iron has the ability to substitute for
zinc in the ERDBD as demonstrated by mobility shift and methylation
interference assays of iron finger, which show specific recognition of
the estrogen response element. The DNA binding constants for both in
vivo and in vitro iron-replaced zinc fingers were similar to that of
the native finger. Atomic absorption analysis revealed a ratio of 2:1
iron atoms/mol of ERDBD protein, as found for zinc in the crystal
structure of native ERDBD. More importantly, we demonstrate that iron
finger in the presence of H2O2 and ascorbate generates highly reactive
free radicals, causing a reproducible cleavage pattern to the
proximate DNA, the estrogen response element. The deoxyribose method,
used to detect free radical species generated, and the resultant
cleaved DNA ends, caused by iron finger, suggest that the free
radicals generated are hydroxyl radicals. Due to the close proximity
of the zinc finger to DNA, we postulate that iron-substituted zinc
finger may generate free radicals while bound to genetic regulatory
response elements, leading to adverse consequences such as
iron-induced toxicity and/or carcinogenesis.
MeSH Terms:
* Base Sequence
* Cloning, Molecular
* Comparative Study
* DNA Damage*
* DNA-Binding Proteins/metabolism
* DNA-Binding Proteins/biosynthesis
* DNA, Bacterial/metabolism
* DNA, Bacterial/chemistry
* Escherichia coli/metabolism
* Escherichia coli/growth & development
* Free Radicals/metabolism
* Human
* Iron/pharmacology
* Kinetics
* Methylation
* Models, Molecular
* Molecular Sequence Data
* Nucleic Acid Conformation
* Oligodeoxyribonucleotides
* Protein Structure, Secondary
* Receptors, Estrogen/metabolism
* Receptors, Estrogen/biosynthesis
* Recombinant Proteins/metabolism
* Recombinant Proteins/biosynthesis
* Support, Non-U.S. Gov't
* Time Factors
* Zinc/physiology
* Zinc Fingers*
Substances:
* Zinc
* Iron
* Recombinant Proteins
* Receptors, Estrogen
* Oligodeoxyribonucleotides
* Free Radicals
* DNA, Bacterial
* DNA-Binding Proteins
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Subject: zinc/iron
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Effects of Trace Elements Supplementation on Measures of Nutritional Status
Effects of supplementation with zinc (30.4 mg/d), copper (3.4 mg/d),
and chromium (241 ug/d) on alkaline phosphatase, serum ferritin,
hemoglobin, and plasma and erythrocyte copper, iron, and zinc were
examined in apparently healthy adults over the age of 50. Differences
were found between males and females within supplement groups. Serum
ferritin decreased significantly during and following zinc
supplementation in males. Total hemoglobin increased significantly
from baseline to four weeks post supplementation in chromium and
copper supplemented females. Alkaline phosphatase decreased from
baseline to four weeks post supplementation in all groups. The
decrease was significant in the mineral supplement groups except for
females receiving zinc--but not in the placebo group. Plasma zinc
increased significantly in zinc supplemented males and during
supplementation and in copper supplemented females from the end of
supplementation to four weeks post supplementation. In the copper
group, plasma copper decreased during supplementation in females but
was not significantly different over time in males, while in the
chromium supplemented females plasma copper increased at eight weeks
of supplementation. These results support the importance of examining
the interactive effects of minerals in both males and females.
Sponsor: Agricultural Experiment Station
PI: Andrea Arquitt
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