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Q J Med 2003; 96: 950-951
© Association of Physicians 2003; all rights reserved.


Correspondence

Severe back pain, depression and psycho-organic syndrome

Sir,

Altered mental activity is a common symptom of hypopituitarism. The most frequent causes of acquired hypopituitarism are pituitary tumors, empty sella, infiltrative or vascular disorders or cranial radiation therapy. We describe a patient with a classical clinical presentation and laboratory findings for a hypopituitarism, but with an extremely rare aetiology.

A 69-year-old woman was referred to the clinic in May 2000 because of progressive debilitation, depression and psycho-organic syndrome. In May 1999, a peridural catheter was placed for continuous administration of morphine (2.5 mg/day) to relieve long-lasting, severe lumbo-vertebral pain of degenerative origin. Since the autumn of 1999, the patient had fallen into a progressive condition of generalized tiredness, inactivity, depression, and mental confusion. On examination, she was debilitated and disorientated, with phases of hallucinations. Cardiopulmonary examination was unremarkable. Neurologically, there was no focal deficit, but deep tendon reflexes were delayed. A fine, pale skin and a loss of the outer third of eyebrows were noted (Figure 1). The diagnosis at admittance was psycho-organic syndrome and major depression.



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Figure 1. Patient in May (above) and November (below). Reproduced with the patient's permission.

 
Blood chemistry and haematology were normal. Lumbar puncture showed a normal pressure; examination of the clear fluid revealed normal chemistry and no micro-organisms. Serum levels of free T4(4.6 pmol/l, normal 9–23 pmol/l), total T3(0.6 nmol/l, normal 1.2–2.6 nmol/l), and of morning (0800 h) cortisol (116 nmol/l, normal 170–800 nmol/l) were low; cortisol increased to 543 nmol/l 30 min after intravenous injection of 250 µg corticotropin. Basal levels of TSH and ACTH were 0.42 mU/l and 5.1 pmol/l, respectively, and gonadotropins were also low, despite the patient's postmenopausal condition. Insulin-like growth factor I (9 nmol/l, normal 16–60 nmol/l) was also decreased, consistent with growth hormone deficiency and hypopituitarism. The patient was treated with cortisone acetate (37.5 mg/day) and, a few days later, thyroxine was added (first 0.05, then 0.1 mg daily). To search for the aetiology of the pituitary failure (in adulthood, most commonly caused by pituitary adenomas), MRI examination of the brain and the sellar region was performed. However, the pituitary gland was normal-sized, without any morphological changes. There were also no signs of malignant, infectious or granulomatous diseases.

The association of neuropsychiatric symptoms and hypopituitarism is well known.1,2 Glucocorticoid and thyroid hormone replacement therapy resulted in a marked improvement of the patient's condition: the debilitation and psycho-organic syndrome disappeared, and the patient's physical appearance and activity clearly improved within 6 months (Figure 1).

Meanwhile, we realised that the unusual feature of our case was the rare aetiology of the pituitary failure. Initial and ongoing efforts to identify a cause listed in the differential diagnosis of hypopituitarism in classical textbooks and review articles1,2 remained unsuccessful, and a presumptive diagnosis of hypophysitis was considered, although no additional arguments in favour of such a hypothesis could be found. An important clue came from the patient's history with long-term intrathecal morphine therapy. Continuous intrathecal morphine is an effective therapy for the management of severe non-malignant pain.3 Such treatment is usually considered safe3 but can, apart from producing analgesia, depress ventilation.4 Moreover, the continuous presence of morphine in the intrathecal space may also have profound effects on pituitary function, particularly on the gonadal, but also on the adrenal and GH axis, as recently reported by Abs et al.5 Even though cause and effect cannot be proven in the case of our patient, it may be the first reported association of prolonged intrathecal morphine administration and complete anterior pituitary failure with a classical syndrome and resolution after hormone-replacement therapy.

It is therefore important to check pituitary function in patients treated with long-term intrathecal morphine.

Internal Medicine Clinica Varini Locarno Switzerland University Hospital Zurich Switzerland

--> T. Bianda, R. Delli Carpini, M. Pagnamenta and C. Schmid

Endocrinology Humaine Clinica Santa Chiara Locarno Switzerland e-mail: bianda.diab{at}bluewin.ch Internal Medicine Clinica Varini Locarno Switzerland University Hospital Zurich Switzerland

References

1. Lamberts SWJ, de Herder WW, van der Lely AJ. Pituitary insufficiency. Lancet 1998; 352:127–34.

2. Vance ML. Hypopituitarism. N Engl J Med 1994; 330:1651–62.[Free Full Text]

3. Anderson VC, Burchiel KJ. A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain. Neurosurgery 1999; 44:289–301.[Web of Science][Medline]

4. Bailey PL, Lu JK, Pace NL, et al. Effects of intrathecal morphine on the ventilatory response to hypoxia. N Engl J Med 2000; 26:1228–34.

5. Abs R, Verhelst J, Maeyaert J, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab 2000; 85:2215–22.[Abstract/Free Full Text]


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