Hypopituitarism

Pituitary infarction may present in many different ways ranging from the entirely silent to the florid neuro-ophthalmological features of apoplexy.[1] It may occur in a normal or an adenomatous pituitary and may be precipitated by haemodynamic changes.[1] We present two cases of panhypopituitarism which developed insidiously as a result of pituitary infarction which occurred during coronary artery bypass grafting.

Case 1

A 57 year old man was referred to our endocrine unit because of impotence and reduced libido. Twenty months earlier he had undergone coronary artery bypass grafting. Before surgery he had had normal potency, but erectile dysfunction and reduced libido occurred immediately after. Three months before surgery he had complained of tiredness; his concentration of free thyroxine was 3 pmol/l and thyroid stimulating hormone was 50 mU/l. Primary hypothyroidism was diagnosed. He was treated with thyroxine, which led to clinical improvement and normalisation of thyroid function before surgery.

Coronary artery bypass grafting was performed alter investigation of exertional chest pain which occurred after myocardial infarction. It was an uncomplicated procedure; the left internal mammary artery was grafted to the left anterior descending artery and the saphenous vein was grafted to the obtuse marginal artery. Recovery immediately after surgery was uneventful and the patient was discharged on the ninth day after surgery despite plasma concentrations of sodium having fallen from a normal preoperative value to 125 mmol/l (normal range 133 to 144 mmol/l). He was readmitted 1 week later with nausea, weakness, a mild fever of 37.5 [degrees] C, and severe hyponatraemia (plasma sodium concentration 114 mmol/l) (table 1). Urea and potassium concentrations were normal. The results of a full blood count were normal and blood cultures were negative.

Table 1 Results of endocrine tests on two patients who developed hyponatraemia after coronary artery bypass grafting

(*) Free thyroxine concentration during treatment with 150 [micro] g thyroxine (see text).

([dagger]) Age related range.

The hyponatraemia was thought to be dilutional and attributed to inappropriate secretion of antidiuretic hormone, although no tests were done to confirm this. The fever gradually resolved without intervention. After 3 days during which fluid intake was restricted, the patient's sodium concentrations rose to 120 mmol/l and he was discharged. He did not complain of headache or any other neurological symptoms.

The patient was referred for endocrine evaluation. The patient had hypogonadotrophic hypogonadism; normal thyroid function (he was taking 150 [micro]g thyroxine daily); undetectable concentrations of prolactin; a low concentration of insulin-like growth factor 1, which suggested a deficiency in growth hormone; and slightly reduced plasma concentrations of sodium. The test results are summarised in table 1.

Dynamic endocrine testing with 250 [micro]g intramuscular tetracosactrin showed a subnormal response which indicated hypoadrenalism. This diagnosis was further supported after testing with metyrapone, which resulted in reduced urinary excretion of 17-hydroxycorticosteroid (results not shown). There was also no gonadotrophin response to luteinising hormone releasing factor, which is consistent with hypogonadotrophic hypogonadism. There was no evidence of diabetes insipidus. The results of dynamic endocrine assessment are shown in table 2. Magnetic resonance imaging of the pituitary confirmed the suspicion of pituitary infarction (fig 1). The patient was treated with hydrocortisone and testosterone and continued taking thyroxine. His condition improved and libido and potency returned to normal.

[Figure 1 ILLUSTRATION OMITTED]

Table 2 Results of dynamic endocrine tests on two patients with hyponatraemia after coronary artery bypass grafting

(*) Luteinising hormone (IU/l) measured for case 1 and follicle stimulating hormone (IU/l) measured for case 2.

([dagger]) Normal cortisol response is > 550 nmol/l at 30 minutes

Case 2

A 61 year old man was referred with an 18 month history of increasing malaise and debility and of reduced libido, potency, and frequency of needing to shave. Five vessel coronary artery bypass grafting had been performed 18 months earlier for extensive coronary artery disease. Venous grafts were inserted to the first diagonal branch of the left anterior descending artery, the first and second obtuse marginal arteries, and the patent ductus arteriosus. A left internal mammary artery was inserted to the left anterior descending artery. The procedure and postoperative course were uneventful, but at discharge on the tenth day after surgery the plasma concentration of sodium was 117 mmol/l (table 1).

Ten days after discharge the patient was readmitted as an emergency with general malaise, anorexia, and fever. His temperature was 39 [degrees] C, his blood pressure was 90/50 mm Hg, and there was dullness to percussion at the right base of chest. He was hyponatraemic with a sodium concentration of 122 mmol/l; urea and potassium concentrations were normal, as were the results of a full blood count. A small right pleural effusion attributed to the previous surgery was seen in a chest x ray; 300 ml of bloodstained aspirate were obtained from the effusion. The patient was treated for suspected pneumonia with broad spectrum antibiotics and intravenous normal saline. He made a gradual recovery, although his fever was slow to resolve. Cultures of the aspirate and of blood were sterile. Titres of mycoplasma, legionella, and viruses did not rise. The plasma concentration of sodium rose slowly but did not reach normal values. By the time of discharge 11 days later his plasma sodium concentration was 130 mmol/l. He did not complain of headache and did not describe any neurological abnormalities.

The results of the routine investigations performed after referral for endocrine evaluation are shown in table 1. These suggest hypogonadotrophic hypogonadism; the low concentrations of insulin-like growth factor 1 suggest growth hormone deficiency with secondary hypothyroidism. Concentrations of prolactin were undetectable and plasma sodium concentration was low. Together with the other supporting data, the subnormal cortisol response to tetracosactrin confirms the diagnosis of hypoadrenalism occurring secondary to pituitary dysfunction (table 2). There was no evidence of diabetes insipidus. Magnetic resonance imaging of the pituitary confirmed the diagnosis of pituitary infarction (fig 2). Replacement treatment with hydrocortisone, thyroxine, and testosterone led to full recovery with restoration of normal sodium concentrations, potency, libido, and drive.

[Figure 2 ILLUSTRATION OMITTED]

Discussion

In both of these cases it seems that pituitary infarction occurred during coronary artery bypass grafting and this led to hyponatraemia shortly after surgery and later development of other symptoms and signs secondary to hypopituitarism. The early hyponatraemia seems to have been the only manifestation of pituitary infarction that reflected a secondary hypoadrenalism. In neither case was hypopituitarism suspected as the cause of the hyponatraemia; the condition remained undiagnosed for over one year after surgery until each patient was seen in our endocrine unit with symptoms of hypogonadism. Both patients responded well to treatment.

Silent pituitary infarction is a more common cause of hypopituitarism than the rare event of apoplexy, although it is unlikely to be diagnosed until symptoms appear. Sheehan described pituitary infarction occurring after postpartum haemorrhage.[2] The features of Sheehan's syndrome are similar to those found in our patients, especially the time that elapsed between presentation and the original pituitary insult. This emphasises the intrinsic vulnerability of the normal pituitary vasculature. Pituitary apoplexy has been described after bypass surgery[3-9] but, in marked contrast to our two patients, each of the 12 cases reported developed acute neuro-ophthalmological problems within 48 hours of surgery. Surgical decompression was necessary in 11 cases; all of these patients had pituitary adenomas and three had been diagnosed before surgery.[4 5 8] The apoplectic presentations were presumed to be secondary to necrosis, haemorrhage, and acute swelling of the pre-existing pituitary turnout.

The clinical presentation in our two patients shows that silent pituitary infarction can also occur during coronary artery bypass grafting in patients with no evidence of a pituitary tumour. It is unlikely that hypopituitarism was present before surgery because of the patients' clinical histories and because, in the first case, primary hypothyroidism with raised concentrations of thyroid stimulating hormone had been diagnosed three months before surgery. At necropsy Kovacs and Yao found that 15% of their patients who died within 10 days of bypass surgery had pituitary necrosis.[10] Pituitary infarction probably arises secondary to the major haemodynamic changes which occur during coronary artery bypass grafting with extracorporeal circulation. While hypotension, non-pulsatile flow, and microemboli may contribute to ischaemia, anticoagulant treatment is probably the underlying factor that causes apoplexy and intrapituitary haemorrhage. Additionally, subtle neurological deficits are quite frequently encountered in patients undergoing coronary artery bypass grafting.[11] These two cases show that pituitary infarction may present silently in patients after coronary artery bypass grafting. Although both of our patients developed complete anterior hypopituitarism, partial hypopituitarism may occur in some cases. Increased awareness of this clinical complication of coronary artery bypass grafting should lead to earlier diagnosis and treatment.

[1] Rolih CA, Ober KP. Pituitary apoplexy. Endocrinol Metab Clin North Am 1993;22:291-302.

[2] Sheehan HL. Simmond's disease due to post-partum necrosis of the anterior pituitary. QJ Med 1939;8:277-308.

[3] Khardori R, Bussing RC, Burns GM, Soler NG. Cardiac bypass surgery with haemorrhagic endocrine sequelae. Postgrad Med J 1987;63:489-92.

[4] Absalom M, Rogers KH, Moulton RJ, Mazer CD. Pituitary apoplexy after coronary artery surgery. Anesth Analg 1993;76:648-9.

[5] Savage EB, Gugino L, Starr PA, Black PM, Cohn LH, Aranki SF. Pituitary apoplexy following cardiopulmonary bypass: considerations for a staged cardiac and neurosurgical procedure. Eur J Cardiothorac Surg 1994;8:333-6.

[6] Shapiro L. Pituitary apoplexy following coronary artery bypass surgery. J Surg Oncol 1990; 44:66-8.

[7] Slavin ML, Budabin M. Pituitary apoplexy associated with cardiac surgery. Am J Ophthalmol 1984;98:291-6.

[8] Cooper DM, Bazaral MG, Furlan AJ, Sevilla E, Ghattas MA, Sheeler LR, et al. Pituitary apoplexy: a complication of cardiac surgery. Ann Thorac Surg 1986;41:547-50.

[9] Peck V, Lieberman A, Pinto R, Culliford A. Pituitary apoplexy following open-heart surgery. N Y State J Med 1980;80:641-3.

[10] Kovacs K, Yao J. Pituitary necrosis following major heart surgery: Z Kardiol 1975;64:52-7.

[11] Harrison MJ. Neurologic complications of coronary artery bypass grafting: diffuse or focal ischaemia? Ann Thorac Surg 1995;59:1356-8.

(Accepted 17 June 1997)

Hypopituitarism may develop secondary to pituitary infarction to pituitary infraction after coronary artery bypass grafting

Department of Medicine, University of Wales College of Medicine, Cardiff CF4 4XN

J S Davies, lecturer in medicine

M F Scanlon, professor of endocrinology

Correspondence to: Dr Davies davies@cardiff. ac.uk

BMJ 1998;316:682-5

COPYRIGHT 1998 British Medical Association
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