Hypopituitarism

Summary

Hypopituitarism is uncommon in elderly people. We report 12 cases of hypopituitarism diagnosed after the age of 60 (range 63-89, mean 74.9) years over a 10-year period. Aetiology was evident in eight cases, viz. pituitary tumour in six and previous post-partum haemorrhage and giant aneurysm of carotid artery in one each. The presentation was often non-specific with symptoms such as lethargy, pallor, falls, urinary incontinence, confusion, fever and flexion contractures. Subtle clues to the condition were missed in four cases resulting in delayed diagnosis. Although levels of pituitary trophic hormones are generally low in this condition, the thyrotrophin (TSH) was normal in seven cases in the present series. Normal levels of serum sodium and potassium did not exclude cortisol deficiency. Hormone replacement therapy resulted in improved quality of life. Physicians dealing with elderly patients should bear this easily treated condition in mind.

Introduction

Hypopituitarism typically presents with pallor, wrinkled skin, loss of body hair and gonadal atrophy. Similar changes occur with the ageing process and elderly people often have multiple pathology that may explain non-specific symptoms. Following an audit review of the management of hypopituitarism patients, the present retrospective study was undertaken to examine the aetiology, clinical presentation, diagnostic pitfalls, and effects of treatment on quality of life in elderly patients.

Methods and Subjects

Case notes of all patients over 60 years of age with a diagnosis of hypopituitarism, presenting to the Department of Medicine for the Elderly at the Sunderland hospitals over a 10-year period to March 1991, were retrieved. Details of aetiology, mode of presentation, results of investigations carried out and treatment given were extracted from the case notes. Further information was obtained from general practitioners and, wherever possible, from the patients themselves in order to assess their quality of life in terms of well-being, mobility and mental state.

Twelve patients (seven women) with a diagnosis of hypopituitarism were available for analysis. The mean age was 74.9 (range 63-89) years. Five patients were diagnosed during their ninth decade of life.

The aetiology of hypopituitarism was pituitary tumour in six and previous post-partum haemorrhage and giant aneurysm of carotid artery in one case each. The aetiology was unknown (idiopathic) in four patients (Table I).

[TABULAR DATA OMITTED]

Presenting features included weakness and lethargy in six cases, hypotension in six, weight loss in five, falls in four, drowsiness and confusion in three each and urinary incontinence and immobility in two cases each. None of the patients presented because of visual impairment. Only one had a visual field defect (right hemianopia) and one had optic atrophy. One patient presented with marked flexion contractures of limbs and generalized wasting, not dissimilar to that seen in malignant disease. One patient presented with hypothermia and another with pyrexia of unknown origin which defied diagnosis for several days until acute cortisol insufficiency (defined as collapse due to hypotension associated with low level of serum cortisol responding to corticosteroid replacement) provided the vital clue.

Results

Table I shows results of endocrine investigations. Serum thyroxine level was low in six cases, normal in the other six, albeit at the lower end of normal range in five of these. Serum level of TSH was low or undetectable in five patients and within a normal range in seven patients. Early clues to diagnosis were overlooked in four cases leading to delay in the diagnosis (Table II).

Table II. Possible causes of delay in diagnosis

Nine patients had eleven episodes of acute cortisol insufficiency. Infection of urinary or respiratory tract was a precipitating cause in six cases. One patient had cortisol crisis twice in 3 months during changes of a long-term indwelling urinary catheter. Subsequent procedures were uneventful when covered by a booster dose of corticosteroid. In three out of 11 instances the serum sodium level was normal and serum potassium level was normal in all but one patient in whom it was low. Hypoglycaemia was observed in two cases.

Two patients with prolactinoma (cases 1 and 2 ) had bromocriptine therapy. Trans-sphenoidal surgery was not considered in any patient with pituitary tumour because of advanced age and multiple coexisting pathologies such as ischaemic heart disease and heart failure.

All 12 patients received corticosteroid replacement therapy and nine patients eventually received thyroxine with resulting improvement in well-being in all cases. Confusion improved in two out of three cases, further falls were not reported in three out of four patients, urinary incontinence improved in two patients, flexion contractures improved dramatically in one patient and fever settled promptly in one patient within 24 hours of instituting the treatment.

Seven patients are still alive (survival time 1-7 years), the rest died of unrelated causes. Autopsy was carried out in one case (case 3) where the pituitary gland was found to be grossly and histologically normal.

Discussion

The prevalence of hypopituitarism in old age is unknown. Though uncommon, the condition may present in old age and physicians need to be aware of the possibility (1). Effects of ageing and multiple disease often modify clinical presentation making diagnosis difficult (2). There is often a simpler explanation for non-specific features such as lethargy, malaise, pallor, wrinkled skin, postural hypotension, loss of body hair, falls and incontinence. It is no wonder that pituitary tumours are infrequently diagnosed over 70 years of age (3)(4) even though commonly found at autopsy (5). Visual-field defect is the commonest detectable abnormality (6) and detailed assessment, by examination of visual fields and ocular fundi, is imperative in all patients with visual impairment before attributing it to ageing or ischaemic changes.

A previous study of pituitary tumours in elderly patients (6) suggested less common occurrence of symptoms related to deficiency of adrenocorticotrophic hormones (ACTH) and TSH in older than in younger patients. However, several apparently non-specific symptoms observed in our patients could be attributed to deficiency of ACTH and TSH.

Endocrine and biochemical abnormalities in hypopituitarism in elderly people may not conform to the commonly expected features in younger patients. Physiological changes in thyroid function associated with ageing (7) and effects of non-thyroidal illness and drugs make interpretation of thyroid function tests in elderly people difficult (8). It has been suggested that the best screening tests for hypopituitarism are serum sodium and thyroxine (2); others have suggested undetectable levels of TSH (1). However, normal concentrations of TSH have been recorded in some patients with hypothyroidism due to pituitary or hypothalamic disease and non-thyroidal illnesses (8)(9)(10). We have found normal concentrations of TSH as well as thyroxine, albeit at the lower end of normal range, in elderly patients with hypopituitarism, suggesting partial or early failure of thyrotropic cells although we are not aware of any studies of progression to complete failure.

An insulin-induced hypoglycaemic test has been used to assess the hypothalamic-pituitary-adrenal axis but this test is hazardous and is usually contra-indicated in elderly patients with other diseases, especially heart disease. For practical purposes, a short synacthen test may demonstrate impaired cortisol production and if necessary a long synacthen test (showing delayed adrenal stimulation) may establish a pituitary cause. A long synacthen test produced delayed adrenal stimulation in two patients with hypopituitarism (cases 1 and 12). Unlike Belchetz (10) we did not find hyponatraemia common; this was not surprising, as mineralocorticoid function is preserved in hypopituitarism.

Replacement with corticosteroid and thyroxine was required in two patients with prolactinoma (cases 1 and 2) despite prior bromocriptine therapy. Although transsphenoidal adenectomy has yielded good results in elderly patients (6), none of our patients was deemed fit for neurosurgical intervention. Most pituitary tumours grow slowly and in the absence of local pressure effects, replacement therapy with corticosteroid and thyroid hormones may be all that is required to improve symptoms as well as general well-being and functional state. Particularly impressive was the complete reversal of flexion contracture in one of our patients, a benefit previously reported (11)(12).

In conclusion, diagnosis of hypopituitarism in elderly patients needs a high index of suspicion, given its non-specific presentation. The search for hypopituitarism is worthwhile as replacement hormone therapy improves well-being and independence.

References

(1.)Hall MRP. The endocrine system--the hypophysoadrenal axis. In: Brocklehurst JC, ed. Textbook of geriatric medicine and gerontology. Edinburgh: Churchill Livingstone, 1985;671-85.

(2.)Anonymous. Pituitary and adrenal disorders. In: Maclennan WJ, Peden NR, eds. Metabolic and endocrine problems in the elderly. London: Springer-Verlag, 1989;125-35.

(3.)Antunes JL, Housepian EM, Frantz AG, et al. Prolactin-secreting pituitary tumours. Ann Neurol 1978;2:148-53.

(4.)Godfrey JB, Caird FI. Intracranial tumours in the elderly: diagnosis and treatment. Age Ageing 1984;13:152-8.

(5.)Kovacs K, Ryan N, Horvath E, et al. Pituitary adenomas in old age. J Gerontol 1980;35:16-22.

(6.)Cohen DL, Bevan JS, Adams BT. The presentation and management of pituitary tumours in the elderly. Age Ageing 1989;18:247-52.

(7.)Havard CWH. The thyroid and ageing. Clin Endocrinol Metab 1981;10:163-78.

(8.)Rae P, Farrer J, Beckett G, et al. Assessment of thyroid status in elderly people. Br Med J 1993;307:177-80.

(9.)Mori T, Imura H, Bito S. Clinical usefulness of a highly sensitive enzyme-immunoassay of TSH. Clin Endocrinol 1987;27:1-10.

(10.)Belchetz PE. Idiopathic hypopituitarism in the elderly. Br Med J 1985;291:247-8.

(11.)Van der Sande JJ, Van Seters AP, Wintzen AR. Dementia with contractures as presenting signs of secondary adrenocortical insufficiency. Clin Neurol Neurosurg 1986;88:53-6.

(12.)Ebinger G, Six R, Bruyland M, et al. Flexion contractures: a forgotten symptom in Addison's disease and hypopituitarism. Lancet 1986;ii:858.

Authors' address(*)

Department of Geriatric Medicine, Sunderland District General Hospital, Kayall Road, Sunderland SR2 7TP

D. K. Chadha

Present address: Department of Medicine for the Elderly, Tickhill Road Hospital, Balby, Doncaster DN4 8QL

(*)Address correspondence to Dr S. C. Tayal, 21 Angram Drive, Grange Town, Sunderland SR2 7RD

Received in revised form 30 November 1993

COPYRIGHT 1994 Oxford University Press
COPYRIGHT 2004 Gale Group