Metabolic and Endocrine Problems in the Elderly

205 Pages·1989·3.906 MB·English

by  W. J. MacLennan MD, FRCP (Glas., Ed., Lond.), N. R. Peden MA, MB, FRCP (Ed.) (auth.)

W. J. MacLennan . N. R. Peden
Metabolic and
Endocrine Problems
in the Elderly
With 29 Figures
Springer-Verlag
London Berlin Heidelberg New York
Paris Tokyo
W. 1. MacLennan, MD, FRCP (Glas., Ed., Lond.)
Professor of Geriatric Medicine, University of Edinburgh, Edinburgh
EHlO 5SB, Scotland, UK
N. R. Peden, MA, MB, FRCP(Ed.)
Consultant Physician and Endocrinologist, Falkirk and District Royal
Infirmary, Major's Loan, Falkirk FK15QE, Scotland, UK
ISBN-13: 978-3-540-19541-2 e-ISBN-13: 978-1-4471-1672-1
DOl: 10.lO07/978-1-4471-1672-1
British Lbrary Cataloguing in Publication Data
MacLennan, W. J.
Metabolic and endocrine problems in the elderly.
1. Man. Endocrine system. Diseases 2. Old persons. Metabolic disorders & nutritional
disorders I. Title II. Peden, N. R. 616.4
ISBN·13: 978·3·540·19541-2
Library of Congress Cataloging-in-Publication Data
MacLennan, W. J.
Metabolic and endocrine problems in the elderlylW. J. MacLennan, N. R. Peden.
p. cm. Includes index.
ISBN-13: 978-3-540-19541-2 (U.S.) 1. Endocrine glands-Diseases-Age factors.
2. Metabolism-Disorders-Age factors. 3. Aged-Diseases. I. Peden, N. R.,
1950-- . II. Title.
[DNLM: 1. Endocrine Diseases-in old age. 2. Metabolic Diseases-in old age.
WK 100MI64m] RC649.M33 1989 618.97'64-dc19 88-38512
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Reprint of the original edition 1989
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Preface
Illness in old age is characterised by vague and atypical presenting features
which are often missed and wrongly attributed to the ageing process. This is
particularly true of endocrine disorders where hypothyroidism may mas
querade as dementia, where electrolyte imbalance may cause lassitude, and
where diabetes mellitus may produce a wide range of complications com
monly associated with ageing. It is our intention that our book provide
straightforward practical guidance in this difficult area by delineating the
effects of ageing on endocrine function and the clinical consequences of
these; and by describing in detail the wide range of presenting clinical fea
tures of endocrine disease in the elderly.
Physicians are also often baffled and misled by the effects of ageing and
disease on laboratory tests used in the investigation of endocrine disease.
Our book describes these changes in detail, and gives guidance on which
tests are most appropriate. Ageing and disease also produce subtle changes
in the response of patients to drugs and replacement, and this is also dis
cussed in detail.
Subjects included separately and in depth include thyroid disease, the
clinical features and treatment of diabetes, postmenopausal changes, bone
disease, fluid and electrolyte imbalance, energy imbalance, and drugs caus
ing endocrine and metabolic disorders. These have been chosen because we
consider that they present problems which are particularly relevant to the
elderly. Many other issues are covered in general textbooks of endocrin
ology and have been omitted.
Several excellent accounts of the endocrinology of ageing are available in
the literature. Most, however, have concentrated on reviewing in depth a
few selected topics. While therefore they are invaluable as sources of back
ground information, they are of less use to the clinician in his management
of everyday problems. We hope that our simple and didactic account will
serve this purpose.
July 1988 W.J.MacL.
N:R.P.
Contents
1 Ageing and Endocrine Function ......................................... 1
2 The Clinical Assessment of Endocrine Disorders in the Elderly. . 17
3 Thyroid Disease .............................................................. 37
4 Diabetes Mellitus: Clinical Aspects ..................................... 63
5 Diabetes Mellitus: Management ......................................... 83
6 Gonadal and Sexual Function ............................................ 103
7 Bone Disease and Disorders of Calcium Homeostasis ............. 111
8 Pituitary and Adrenal Disorders 125
9 Fluid and Electrolyte Imbalance 137
10 Body Build and Nutritional Balance .................................... 153
11 Endocrine and Metabolic Effects of Drugs and Hormonal!
Endocrine Manipulation of Non-endocrine Diseases ............... 169
12 Investigation of Endocrine Disease ..................................... 185
Subject Index ....................................................................... 199
1 Ageing and Endocrine Function
An understanding of the effects which ageing has on endocrine function is funda
mental to the correct interpretation of the clinical and biochemical features of
endocrine disease in old age. In some instances, as in hyperthyroidism, ageing
modifies the physical signs. In others, as in carbohydrate metabolism, ageing
changes the reference values, so that there is the semantic problem of whether
values which are common are also normal.
A phenomenon less frequently appreciated is that in addition to changing
norms, ageing also increases variation. Any description of ageing and endocrine
function which fails to take this into account is an oversimplification.
Hypothalamo-pituitary Function
Ageing is associated with a decline in the hypothalamic concentrations of neuro
transmitters, including catecholamines, y-amino-butyric acid and acetylcholine
(Everitt 1980). Coupled with this, there is a decline in the sensitivity of the
hypothalamus to changing concentrations of some hormones and metabolites. An
example is that the threshold of the hypothalamic appetite centre to the inhibitory
effect of glucose is often elevated in old age (Dilman 1976). Again, corticosteroids
are less effective in suppressing hypothalamic activity in the elderly. The extent to
which this influences anterior pituitary function varies with the hormone involved.
Growth Hormone
Recent studies have shown a decrease in the nocturnal secretion of growth hor
mone particularly during the first 3 h of sleep in elderly as compared with young
men (Prinz et al. 1983) and similar observations have been made in Rhesus mon
keys (Kaler et al. 1986). Serum somatomedin levels also diminish in old age (Pav
lov et al. 1986) and correlate with diminished growth hormone levels (FIorini et al.
2 METABOLIC AND ENDOCRINE PROBLEMS IN THE ELDERLY
1985). Again, though growth hormone responses to hyperglycaemia are unaf
fected by age, men over 40 years of age show reduced growth hormone responses
to growth hormone releasing hormone (GHRH) (Shibasaki et a1. 1984) and a
negative correlation between age and growth hormone responsiveness to GHRH
has been shown in men and women, with circulating oestradiol concentrations
having a significant effect on responses in women (Lang et a1. 1987). This raises
the possibility that a proportion of elderly subjects are growth hormone deficient
with resulting effects on bone and muscle mass.
Thyroid-Stimulating Hormone (TSH)
Around one in ten men and one in four women over the age of 60 have high serum
concentrations of TSH (Table 1.1) (Sawin et a1. 1979). These levels are rarely
associated with low thyroxine levels in healthy old people, and few people with an
isolated serum TSH elevation proceed to hypothyroidism.
Table 1.1. Percentages of men and women with elevated serum TSH
levels (Sawin et al. 1979)
Percentage with Percentage with
moderately elevated markedly elevated
TSH>S <lOmU/l TSH>lOmU/l
Men 8.2 2.7
Women 16.9 7.1
In healthy old people, the standard dose of thyrotrophin releasing hormone
(TRH) stimulates a normal increase in the serum TSH concentration while a post
mortem study has shown that the hypothalamic content of TRH does not change
significantly with age (Ordene et a1. 1983; Harman et a1. 1984; Parker and Porter
1984).
Adreno-corticotrophic Hormone (ACTH) and Beta-endorphin
These anterior pituitary peptides are produced from a common precursor
molecule, pro-opiomelanocortin and are secreted concomitantly (Imura 1985).
The circadian rhythm of plasma ACTH and cortisol is not affected by age
(Rolandi et a1. 1987) but the circadian changes in beta-endorphin levels present in
young individuals disappear in old age. The mechanism of this is unclear.
The response of ACTH to the stress of surgery is similar in young and elderly
subjects (Arnetz et a1. 1984).
Prolactin
In postmenopausal women there is a rise in plasma prolactin concentrations
(Figure. 1.1) (Govoni et a1. 1983). This itself is not of clinical importance, but
AGEING AND ENDOCRINE FUNCTION 3
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AGE IN YEARS
Fig. 1.1. Plasma prolactin level in elderly men (circles) and women (crosses). (After Govoni et al.
1983.)
probably reflects the decrease in pituitary inhibition which follows a reduction in
hypophyseal dopaminergic activity. No such changes occur in men, but an inverse
correlation has been reported between frequency of sexual intercourse and pro
lactin levels in the elderly (Weizmann and Hart 1983). The prolactin response to
surgical stress is reduced in the elderly, particularly in older men (Ametz et al.
1984).
Gonadotrophic Hormones in Men
Plasma levels of luteinising hormone (LH) and follicle stimulating hormone
(FSH) are increased in elderly men (Muta et al. 1981; Deslypere and Vermeulen
1984).
Gonadotrophic Hormones in Women
After the menopause there is a threefold rise in plasma LH concentrations com
pared with a tenfold increase in those ofFSH (Mills and Mahesh 1977). Following
an initial postmenopausal rise in gonadotrophin concentrations, there is a progres-
4 METABOLIC AND ENDOCRINE PROBLEMS IN THE ELDERLY
sive fall in these so that after 30 years they are at about half the maximal levels
(Chakravarti et al. 1976). Surprisingly the gonadotrophin releasing hormone con
tent of the hypothalamus is lower in elderly than premenopausal women (Parker
and Porter 1984).
Pineal Gland
Plasma melatonin concentrations in the elderly are about half those found in
young adults while at all ages, melatonin secretion increases at night and falls by
day. Maximal levels in old people occur in October, whereas in the young these
occur in January, suggesting an age related change in the hypothalamic control of
secretion (Tointon et al. 1984). Histological studies have shown no change in the
structure or function of pinealocytes.
Thyroid Gland
Though total serum thyroxine levels are unchanged there is a marginal reduction
in serum total tri-iodothyronine levels (Caplan et al. 1981; Harman et al. 1984).
This coupled with decreased degradation rates of thyroxine and tri-iodothyronine
suggests an overall reduction in thyroid hormone production. The only clinical
relevance of these changes is that, in establishing ranges of "normal" for tri
iodothyronine, it is important to take age into account.
Adrenal Cortex
As noted above, the circadian variation in serum cortisol concentrations persists
with ageing but there is a reduction in the 24-h excretion of urinary corticosteroid
metabolites, suggesting that there may be a reduction in cortisol synthesis in the
elderly. Ageing also is associated with a decline in the metabolic clearance of cor
tisol (Everitt 1980). Under conditions of stress, however, there is no evidence of a
diminished adrenocortical reserve and indeed a standard dose of ACTH often
produces a higher peak plasma concentration of cortisol in old age than in youth.
After the menopause a decline in ovarian function results in the adrenal cortex
becoming the principal source of oestrogens and androgens. Thereafter there is a
continuing decline in the cortical synthesis of steroids such as dehydro-epiandro
sterone, 17-hydroxypregnenolone and pregnenolone; whereas there is an actual
increase in androstenedione, 17-hydroxyprogesterone and progesterone produc
tion.
AGEING AND ENDOCRINE FUNCTION 5
Gonadal Function in Women
After the menopause there is a dramatic fall in both oestrone and oestradiol
(Chakravarti et al. 1976) (Fig. 1.2). Thereafter there is a further progressive
decline in oestrone levels whereas oestradiol levels remain unchanged or even rise
marginally. The effects of these changes on physiological function in general and
bone metabolism are discussed in Chaps. 6 and 7.
100
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~1 2-3 5 10 20 30
YEARS AFTER THE MENOPAUSE
Fig. 1.2. Geometric mean concentrations of oestrone (circles) and oestradiol (crosses) in women after
the menopause. The geometric mean concentrations of oestrone and oestradiol before the menopause
are 439 pmolll and 250 pmolll. (After Chakravati et al. 1976.)
After the menopause there is a change in androgen levels, characterised by a
decline in the serum androstenedione to 40% of the initial concentration (Studd
and Thorn 1981). In contrast, testosterone levels remain unaffected and its
metabolism may contribute to the maintenance of 17-beta-oestradiol concentra
tions. The clinical relevance of these changes is uncertain.
Gonadal Function in Men
There is conflicting evidence on whether or not serum testosterone levels decline
with increasing age and this may in part relate to whether populations studied have