Arch. Gerontol. Gerietr. suppl. 5 (1996) 355-362 0167-4943/96615.00 0 1996 Elsevier Science Ireland Ltd. All rights resewed 355

HORMONE LEVELS IN CENTENARIANS

M.V. BALDELLI, P. ZUCCHI, J.M. PRADELLI, V. MONTANINla

and M.C. DeSANTISa

Department of Internal Medicine, Chair of Geriatrics and Gerontology; aChair of Endocrinology, University of Modena, Viale Vittorio Veneto, 9, I-41100 Modena, Italy

SUMMARY The serum profiles of total triiodothyronine (T ), free thyroxin (fT ),

thyroid stimulating hormone (TSH), cortisol, prolact?n (HPRL), parathormjne (PTH), osteocalcin and growth hormone (CH) were measured in a group of 12 centenarians and compared to the values of a control group of twenty-nine sub- jects, aged 67-98 years. The study was aimed at revealing whether there are appreciable differences or age-related modifications in the hormone status of healthy control elderly and the centenarian population. In this series, the modi- fications in hormone levels were unremarkable, and the serum levels of the stu- died hormones in centenarians often fell within a range considered to be normal for the younger age classes.

Keywords: hormone levels of centenarians,

INTRODUCTION

The blood chemistry of centenarians and ultracentenarians can provide data

of gerontological interest, even if these values cannot always be compared to

those of the total population, since centenarians represent a highly selected

group of individuals (Nemeth et al., 1990). In fact, laboratory data can be

particularly difficult to interpret in very old subjects. Namely, an age-related

pattern of circadian rhythm of hormone secretion has been reported in man, but

the range of values considered normal is often derived from populations in which

elders, and especially the oldest old, are only marginally represented.

So far no single factor has been discovered that can predict longevity.

Nonetheless, several consistencies have been detected in persons surviving until

very late age, such as a family history of longevity, above average schooling,

active social network and also good general health (Beregi, 1990; Baldelli et al.,

1991; IPSEN Fondation, 1991; Taeuber and Rosenwaike, 1992).

In this paper, representing a part of a larger ongoing study on centena-

rians and ultracentenarians, we evaluated the pattern of several hormone levels

in the context of a multidimensional assessment of the oldest old humans and

compared them to those found in healthy control elderly population.

356

PATIENTS AND METHODS

We studied 12 centenarians ranging in age from 100 to 104 years (mean age

101 + 1.3 years), 2 males and 10 females, and 29 healthy control subjects aged

67 to 98 years (mean 81.8 + 6.81, 9 males and 20 females. -

The 29 subjects aged 67 - 98 years were selected according to the SENIEUR

protocol (Ligthart et al., 1990). The subjects of both groups underwent the fol-

lowing tests: (i) the Geriatric Depression Scale (CDS) (Yesavage et al., 1983).

in order to evaluate their affective status; (ii) the Mini Mental State Examination

(MMSE) (Folstein et al., 1975), in order to evaluate their cognitive functioning.

The body mass index (BMI) was also calculated, in order to obtain a measure of

their nutritional status. In addition, serum calcium, phosphorus, creatinine and

urea levels were determined, and urine analysis was also performed.

An additional blood sample was also taken, and a battery of hormones on

the serum was determined, including total triiodothyronine (T3), free thyroxin

(fT4), thyroid stimulating hormone (TSH), cortisol, prolactin (HPRL), parathor-

mone (PTH), osteocalcin and growth hormone [GH). Hormone levels of T3, fT4

and TSH were measured by CIBA Corning Automated Chemiluminescence Systems

[ACS 180) (Fernandez-Ulloa and hlaxon, 1989); prolactin and GH by Time-Resol-

ved Fluoroimmunoassay System, model Delfia (Wallac, Sweeden) (Lovgren et al.,

1985); cortisol was determined by Enzyme Immunoassay Kit using Novopath model

instrument (Biorad, USA) (Tietz, 1986); PTH by lmmunoradiometric Assay

(I.R.M.A., Nichols, IJSA) [Rodbard and Hutt, 1974), and osteocalcin by Radio-

immunoassay (RIA) Kit distributed by Diagnostic System Laboratories Inc. (USA)

[Yalow and Berson, 1971).

RESULTS

The affective status of all of the studied subjects fell within normal limits of

the GDS, varying from 5 + 1.7, (range 2-8), for the centenarians and 4.6 + 1.8 - -

(range from 2-9) for the controls.

The variations in MMSE score did not reveal cognitive deficits in the control

group: their mean was 28.3 + 1.8, (range 27-30), - and a good cognitive profile

was also encountered in the centenarians: their mean was 26.2 + 2.7 (range 24- -

29).

The BMI values, although were variable, fell within the normal limits: 23 +

3.6 (range 19-31) in the centenarians, and 25.9 + 2.9 (range 22-31) in the con-

trol group.

Serum calcium and phosphorous levels were normal (calcium: 9.5 + 1.3 -

mgidl, range 8.5-10.8 in centenarians, and 9.8 + 1.7 mg/dl, range 8.5-11 in

controls; phosphorous: 3.7 + 1.8 mgldl, range 2.5-5.1 in centenarians and 3.4 +

2.1 mgldl, range 2.5-5 in controls).

357

The majority of centenarians had normal serum creatinine and urea (crea-

tinine: 1.2 + 0.6 mg/dl, range 1.1-1.5; urea: 48.8 + 3.2 mgldl, range 42-58);

all of the control subjects had normal values (creatinine: 1 .2 + 1 .l mg/dl, range

0.6-l .3; urea: 42.2 + 3.8 mg/dl, range 28-50). Urine analysis did not reveal any

remarkable alteration in either of the groups.

The series of centenarians we examined included subjects with a limited his-

tory of bone fractures, all had healed and calcified well; the subjects had no

episodes of kidney stones, peptic ulcers or any disorders with large bone re-

sorption (such as Paget’s disease or severe osteoporosis).

The hormone levels observed in the centenarians, and in the control elderly

group are presented in Figures 1 and 2, respectively. For comparison, the

generally accepted normal values (n.v.) are also reported in both figures.

100

* 50

16

14

12

10 *

a

0 6 T3 fT4

4.35

3.35

2.35

1.35

0.35 TSH

t GH

n.v RD.200 ng/lOO ml n v 6 l-16.7 pglml “.V 0.35-4.5 mlU/ml n.v. O-6 5 nglml

251

201

15

10 *

5' Coftisol

n.v. 5.5-25 mcg/lOO ml

12

10

a

6

4 f

2’ Osteocalcin

n.v 2-12 rig/ml

150

130

110

90

70

50

30

IO PTH

n.v. IO-65 pglml

2% 20

15

10

5

0 HPRL

“ . “ . M: 2.4-11.5 F: 2.7-14.6

nglml

Figure 1. Mean hormone levels found in the centenarians (12 subjects). Abbre- viations are explained in the text.

The T3 level tended to be lower than the normal average in centenarians,

whereas it remained nearly normal in the control old group; fT4 and TSH were

normal in both groups. GH, cortisol and osteocalcin were normal in both groups.

On the contrary, PTH was nearly normal in the controls, whereas it was

appreciably increased in centenarians. HPEL was variable; some subjects in both

358

groups tended to have higher than normal HPRL levels, and this trend, found in

both groups, was more emphasized in the centenarians.

200 16

180 14

160 12

140 *

IO * 120 100 8

80 6 T3 fT4

n v. 80-200 ng/lOO ml n.v 6.1-16.7 pglml

2.35

0.35 TSH

n.v. 0.354.5 mlU/ml n.v. O-6.5 rig/ml

8

6

4

2

0 * GH

25

20

15

10 *

51 Cortisol

n.v. 5.5-25 mcg/lOO ml

2' Osteocalcin

n v. 2-12 nglml

150

130

110

90

70

50

30

10 *

PTH n.v. lo-65 pg/ml

25

20

15

IO

5

0 HPRL

".". M: 2.4-11.5 F: 2.7-14.6

rig/ml

Fi ure 2. Mean hormone levels found in the control elderly group (29 subjects). 7x%5-. revlatlons are explained in the text.

DISCUSSION

Our findings are in agreement with other reports on the general elderly po-

pulation and on centenarians (Klinger, 1989; Curb et al., 1990; Baldelli et al.,

1991; Brock, 1991; Mizutani and Shimada, 1992).

Several studies have examined thyroid function during aging and in cente-

narians (Laszlo, 1990; Mariotti et al., 1992). The centenarians have a decrease

in plasma T3 levels and stable fT4 levels (Gregerman, 1967; Rubinstein et al.,

1973; Burrows et al., 1975; Larsen et al., 1981). The behavior of TSH was more

variable, and it has been reported to remain unchanged, to increase or to de-

crease (Jacques et al., 1987; Kaiser, 1987; Runners et al., 1991; Jouanny et

al., 1993). In our series, a downward trend of T3 was observed, whereas fT,,

and TSH remained at normal levels, except for one subject who had a reduced

TSH level. None of these subjects had overt signs of thyroid disease or a me-

dical or family history positive for thyroid disease, nor were they taking

thyroid-active drugs.

359

Moreover, the subjects were not depressed as evaluated with the CDS, nor

did they have any specific cognitive impairments.

The BMI, though variable, fell within normal limits; none of the subjects

was extremely underweight or obese.

The comparison with the control group showed an appreciable overlap of the

fT4 and TSH values (one subject had low TSH levels); instead the T3 pattern

differed since all subjects in this series had normal values, and we did not find

the decline in total T3 observed in centenarians.

Several studies have investigated the effects of aging on the GH levels

(Dud1 et al., 1973; Sun et al., 1984; Ho and Hoffman, 1993; Slootweg, 1993).

During normal aging, GH levels have been reported either to remain unchanged

(Shibasaki et al., 1984; Sohmiya et al., 1992) or to fall (Sun et al., 1984, Brock

1991; Ciusti et al., 1992). In our study population the CH level of centenarians

was basically within the normal limits; none of the subjects was on GH replace-

ment therapy. GH in controls behaved similarly.

Cortisol levels are reported not to change during normal aging (Brock,

1991: Giusti et al., f992), and this was supported by the cortisol levels in our

control and centenarian subjects (one centenarian had values slightly below the

normal).

In contrast, osteocalcin has been reported to increase during aging (Nor-

din, 1976). The data from our series did not confirm this trend, since osteo-

calcin levels remained normal in all subjects.

The PTH levels were different in the two groups. Serum PTH level increa-

ses with aging (Orwell and Meyer, 1986; Kochersberger et al., 1990). and in-

deed, it increased in some of the subjects we examined. The increase in PTH le-

vels was limited only to 10.3 % of subjects in the control group, but it was

found in more than 58 % of centenarians. Calcium and phosphorus levels were

normal in all subjects with elevated PTH. as was the kidney function.

Serum prolactin levels vary with aging (Sun et al., 1984). It has been re-

ported to decrease, especially in males (Brock, 1991; Ciusti et al., 1992). In

our subjects, prolactin levels were variable: 63.6 “a of the subjects had normal

levels, and 27.2 8 showed increased ones. This trend was also observed in con-

trols, where 10.3 8 of the subjects had increased serum prolactin levels. HPRL

activity was below normal in one centenarian and in none of the controls. Thus,

the behavior of our series differed in part from that considered physiological

during aging since the subjects maintained satisfactory HPRL levels.

CONCLUSIONS

Our findings in this centenarian population suggest that aging per se does

not lead to radical modifications of hormone levels. Indeed, comparison with

360

healthy elderly subjects aged 67-98 years indicated generally overlapping hor-

mone profiles in centenarians, at least for those tested, i.e., the serum levels

considered normal for the younger age classes are maintained in the oldest old

subjects.

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