Psychosis in a patient with hyperkalemic periodic paralysis

Medical Psychiatric Rounds Clinicians of alI specialties are invited to submit reports of clinical conferences of individual cases that illustrate the application of psychological principles to the understanding, diagnosis, and management of all varieties of illness. Editorial consideration will be given especially to reports that demonstate how psychiatry and medicine relate to primary care. Manuscripts should be sent directly to Norman B. Levy, M.D., Editor of Medical Psychiatric Rounds (See Information to Authors for address).

Psychosis in a Patient with Hyperkalemic Periodic Paralysis Peter L. Jenkins and Geraldine Shaw Abstract: Presentation of an unusual case of a hyperkalemic periodic paralysis patient who developed a psychotic illness during the course of treatment is made in a conference format. The differential diagnosis of this psychotic episode together with some information regarding hyperkalemic periodic paralysis are discussed. The case illustrates the benefits of close cooperation between medical and psychiatric teams in the management of the psychotic patient with medical illness.

The following is excerpted from the weekly MRCPsych course case conference at Whitchurch Hospital, Cardiff. This is a discussion of an unusual and interesting case of hyperkalemia. Dr. Shaw: Mrs. H. is a 35-year-old lady. In 1982, she was found to be thyrotoxic and an autoimmune thyrotoxicosis was diagnosed. She was treated with radioiodine but was rendered myxedematous, and thyroxine replacement was instituted. Her second autoimmune phenomenon appeared in 1984 when she was admitted to the hospital with complaints of fatigue and angina. The Hemoglobin and platelet count were low. She was Coombs’-positive and red cell autoimmune antibodies were found. A diagnosis of Evans syndrome was made [l]. This is an autoimmune hemolytic anemia associated with thrombocytopenia and supposed to be steroid responsive. She was, therefore, administered steroids in high dosage and also folic acid. Her response was good; her blood count and platelet count rose. She was maintained on prednisolone for a number of months and then the dose was reduced. Later on that year she became ill again From the University of Wales College of Medicine (P.L.J.) and Singleton Hospital, Swansea, U.K. (G.S.). Address reprint requests to: Peter L. Jenkins, M.D., Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom.

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and she was readmitted. A midstream urine (MSU) revealed a growth of proteus and an IVP showed a left staghom calculus. She had a left nephrectomy and the surgeons performed a splenectomy at the same time. Subsequently, the prednisolone was stopped and her blood count stayed normal. She seemed to have responded to splenectomy. Next, she was found to be hyperkalemic. Repeated electrolytes confirmed a raised potassium level. She was admitted in March 1987 for assessment and was found to have a serum potassium of 8.3 (normal ~4.8). We were concerned because of the danger of arrhythmias and cardiac arrest. At that time she was complaining of some paresthesia in her hands and feet, and had polyuria and polydipsia. She experienced her first full-blown attack of paralysis associated with hyperkalemia in April. The attack lasted 6 hours, starting with paresthesia in her hands and her feet, which slowly ascended to her waist. Oddly, her tendon jerks remained, although she was paralyzed; obviously she became very panicky with the attacks. She was initially treated with familiar regimes, such as insulin and dextrose. Instead of her potassium falling, it rose even further to 9.2 mEq/L. Patients with aldosterone deficiency may show a paradoxical rise after dextrose infusion due to solvent drag. In this patient, aldosterone levels rose appropriately with serum potassium (K+ 7.35 Aldosterone 15 ng/dL, K’ 4.2 Aldosterone 9.5), excluding aldosterone deficiency as a cause of the hyperkalemia. At that time, she was acidotic, although we were not certain whether the acidosis was a consequence of the hyperkalemia or whether it preceded the episode. We therefore decided to initiate peritoneal dialysis. This rapidly brought her potassium level down to normal. Tests such as urinary potassium and fecal potassium were perGeneral Hospital Psychiatry 12, 12, 56-61, 1990 0 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010

Psychosis with Hyperkalemic Paralysis

Table 1. Treatments

for hyperkalemia

Intravenous dextrose and insulin Bicarbonate Calicium resonium Calcium chloride Forced diuresis-saline and frusemide Salbutamol Acetazolamide Peritoneallhemodialysis

formed because we considered self-administration of a potassium load. The fecal potassium was nor-

mal. This does not exclude self-administration of a potassium load that would require measurement of potassium excretion on a fixed diet and response to potassium loading. Urinary potassium was normal on several occasions when serum levels were greater than 8 mEq/L. During loading, attaining levels of 7.1 mEq/L, urinary levels were also normal. These results were felt to exclude self-administration. Because she had previously been treated with steroids and had a history of autoimmune disease, we wondered whether there was a possibility of an Addisonian crisis, as it is one of the causes of high potassium. Hence, we took serum cortisols and treated her empirically with hydrocortisone, which brought about improvement, but the serum cortisols were 50 Fg/dL prior to treatment, disproving this theory. Since the termination of cortisol replacement, she has had numerous attacks of hyperkalemia and we have used most treatments described unsuccessfully (Table 1). Treatments such as salbutamol, acetazolamide, and dialysis are not normally used other than for people with hyperkalemic periodic paralysis (HPP). Steroids have been the only successful treatment. It should be noted that several of her attacks did resolve spontaneously. A typical attack lasts for 5-6 hours. During an attack, the serum potassium rises steadily to a peak, and during the rise the patient experiences an onset of tingling. At the peak she develops ascending paralysis that slowly resolves. In June, Mrs. H. had the first attack that was associated with ventricular tachycardia, and at that time we administered an antiarrhythmic, amiodarone. In July while on a maintenance dose of amiodarone, she had an attack of ventricular tachycardia with hyperkakmia and the dose was increased again to 250 mg amiodarone t.i.d.; at no time, however, were the serum lev-

els in the toxic range. In July she also had a single episode of acute psychosis for which we consulted the psychiatrists. She was transferred for assessment to an inpatient ward and amiodarone treatment was terminated. She returned after being started on prednisolone and the frequency of her attacks was reduced. We began reducing her steroids and the paralytic attacks returned. She is now stable on 30 mg of prednisolone a day, plus azathioprine used as a steroid-sparing agent and has not had an attack involving paralysis for 3 months. She has had one attack about a month ago at home with paresthesia only, which lasted about 6 hours and was selflimiting. More than 20 separate attacks occurred over 6 months, and as each attack was associated with elevated potassium, we made a diagnosis of hyperkalemic periodic paralysis on clinical grounds, although this case is atypical. Features that make this case different from previously described HPPs [2] are the later age of onset, preservation of tendon jerks, paresthesia-whereas usually one finds myotonia. (Normally with HPP, serum potassium rises to about 6 or 7 and is not ordinarily associated with cardiac arrhythmias.) Attacks are not precipitated by the usual factors: in patients with HPP, cold, stress, and exercise precipitate an attack. We have identified no precipitants in the present case and this patient does not respond to standard treatments. The patient’s attacks seem to be controlled on steroids, and when these were discontinued she had numerous attacks, which again stopped following reinstitution of steroid treatment. The mechanism of this response is obscure. In vitro incubation of serum and potassium with her own cells was performed with prednisolone absent and present (Fig. 1). With a normal person’s cells, potassium would be transported into the cells due to the operation of the sodium-potassium pump and serum potassium would fall. In Mrs. H., such an effect is seen only when prednisolone is present. This is suggestive of an abnormality at the sodiumpotassium pump accounting for her periodic hyperkalemia. Although we had no clinical evidence of family history of paralysis, the patient has three children and the youngest child’s cells show the same phenomenon as those of Mrs. I-T., although

the child has no symptoms. Regardless of these atypical findings and the fact that steroidresponsive HIV’ has not been previously reported, we found no evidence from our investigations of 57

I’. L. Jenkins and G. Shaw

7.1

7.1

Without ~SOlOne

With prednisolone

1 any other cause such as self-administration of a potassium load and felt confident in diagnosing HPP. Dr. Peter Jenkins: Pertaining to the psychiat-

ric component of this patient’s presentation, I saw her sometime after this event and she described what happened at the onset of her acute psychosis. She said of her doctor that morning, “He told me that if my potassium goes up it will kill me. At that point I developed a violent hatred of Dr. L. I thought I was just one of his rats in an experiment.” This is a very clear description of the psychologic shock that led to sudden onset of psychosis and breakdown of the patient’s ego. She later felt that all hospital staff were in league to harm her; she heard voices and strange men talking about her. They controlled her thoughts, actions, wishes; they put thoughts into her mind, and she saw a vision of a green heaven. On the day after her admission, she dressed and dashed for the fire escape, needing restraint by the nursing staff. At that time, she was not really able to give a good history. This is her family history: She was divorced in 1983 during the course of one of her paralytic admissions, and her younger daughter took an overdose when her grandmother was looking after her while the patient was in hospital. Mrs. H.‘s natural father deserted the home when she was aged 7, and she has a paternal aunt who is a long-term inpatient at a psychiatric hospital with a diagnosis that is uncertain. Another aunt suffers from an obsessive-compulsive disorder that is, as you know, sometimes a defensive mechanism for psychosis. 58

2-

TimeHours

Figure 1. Incubation of cells with and without prednisolone.

When psychotic, she wanted to escape and was committed. Her experience of these events was essentially an enactment of her delusional fears about the staff. The entire period we are talking about lasted approximately a week. In 1977, she had severe postnatal anxiety. This was treated with diazepam. In 1981, she was given radioiodine and 2-3 years later she became anxious and agoraphobic, and developed sleep problems; she was given lorazepam. Then 2 or 3 years later she was given thyroxine because she had become hypothyroid. In 1984, what she described as a blood disorder also occurred, and she was given diazepam at this point by her general practitioner. In March 1987, the first of these paralytic periods occurred. We have at least four different possible causative agents for psychosis: the steroids, the thyroxine, paralysis and electrolyte disturbances, together with some form of predisposition as indicated by her psychiatric history. When I saw her, her mental state was normal. She was alert and oriented with appropriate mood and affect. She described disturbed sleep with very prominent dreams-men with green ears, rabbits with sunglasses (she meant by this huge-sized rabbits-slightly more abnormal). Her appetite, however, was o.k. She described no formal thought disorder at this time-although she recalled that she previously had had thought insertion, withdrawal, echo, running commentaries, and so on, all Schneiderian symptoms. In her mental state, she complained of some fuzziness of memory. Her Mini-Mental State score was 27 out of 30, on the

Psychosis with Hyperkalemic Paralysis

following medication: haloperidol 6 mg at night,

temazepam 20 mg, 45 mg of steroids (which were being reduced), and thyroxine. I would like to throw open the discussion about this lady‘s illness. Dr. Nahla Jarnil:’ This lady responded to steroids. Could this be a collagen disease like SLE? Dr. Shaw: The fact that it is responsive to steroids would suggest that it is immune-based, but there is no evidence that she has a collagen vascular disease. Auto-antibodies, rheumatoid factor, and ANF are all negative. Only TSH receptor antibodies are positive, consistent with Graves’ Disease. The incidence of depression in patients with SLE is quite high and sometimes the local vasculitic response can cause temporal lobe problems, epilepsy, and psychotic phenomena [3]. Dr. Sudud Jawad? Could a temporal lobe epilepsy focus due to electrolyte imbalance be considered in the differential diagnosis for this lady? Dr. Shaw: She has not had clinical features of TLE. TLE can, of course, produce a psychotic picture. Dr. Ryland Jones:3 Was the dose of prednisolone increased just before the psychosis? Dr. Shaw: No, she was on a decreasing dose. Dr. June S~~iley:~I understood that steroids tended to precipitate psychosis when the dose was changed. Dr. Peter Jenkins: It is change in the doses that leads to precipitation [4]. Dr. Gerald O’Mahoney:’ Patients on steroids are quite a problem because many people are on steroids. It is very hard to know what loading or weighting to give it, it is such a common finding on the ward. Dr. Peter Jenkins: In this case, we can rule out steroids because she is still on them and is much better. And she has had them before when she had Evan’s syndrome and she did not have any psychological concomitants then. Dr. Muthildu Hernandezf I saw this patient as an emergency consultation. The problem then was that it was impossible to get a word out of her. It was impossible to get any history or anything. ‘Senior House Officer in Psychiatry, University of Wales College of Medicine. *Registrar in Psychiatry, University of Wales College of Medicine. 3Registrar in Psychiatry, University of Wales College of Medicine. 4General Practitioner, University of Wales College of Medicine. 5Registrar in Psychiatry, University of Wales College of Medicine.

Dr. Peter Jenkins: At that time she was very disturbed and obviously virtually catatonic from your description. Although she may have been uncooperative when she was actually seen, she was in fact fully conscious and having a subjective experience that was terrifying and frightening. Catatonia is often associated with organic brain syndromes [5]. Dr. Phil HuckZe:7Another thing to consider as a liaison psychiatrist is the possibility that she was hypothyroid, which, of course, she was not, was she? Dr. Shaw: On three or four occasions she was biochemically euthyroid. The only abnormality is hyperkalemia . Dr. Peter Jenkins: I have seen several people with altered potassium levels and psychiatric symptoms. One individual presented with a severe depressive state, having overmedicated himself; one had episodic paralysis after carbohydrate ingestion, which he used to get after drinking “real ale”; and another, who was of Bedouin extraction, had a familial problem and became quite upset and inappropriate in her behavior when she had hyperkalemia. Dr. Shaw: Carbohydrate ingestion is usually used for treatment of hyperkalemic periodic paralysis. On the renal unit, you do see a lot of hyperkalemia, and people with renal failure often get psychiatric disturbances [6]. With some of them it may be potassium, but if they are uremic then you are more likely to attribute it to uremia. Dr. Rujah JiZani? Were there any depressive features in this lady? Dr. Shuw: I think she had a predisposition towards depression. She has had a very difficult life. She has always suffered from domestic violence. Two weeks ago her stepfather, who was supportive, was murdered. Despite these stresses she appeared to cope well. Her children are going to have a lot of difficulty. She has been in and out of hospital for months; weekend leaves have been terminated as an emergency because she was having at attack. The effect on her children of seeing their mother during an attack, not able to move, not able to get to a telephone, must be very distressing for them. I am not surprised her little girl has taken two overdoses. %enior House Officer in Psychiatry, University of Wales College of Medicine. Senior House Officer in Psychiatry, University of Wales College of Medicine. ‘Senior House Officer in General Medicine, University of Wales College of Medicine.

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P. L. Jenkins and G. Shaw

Dr. Peter Jenkins: Suicide and parasuicide in such a young child is extremely rare [7l. In a survey of all suicides in the United Kingdom between 1962 and 1968 [8], there were no suicides under 12 years, yet this girl’s second attempt needed 5 days of intensive care. Dr. Richard Jenkins:9 You said this lady was on benzodiazepines and that is another complicating factor, is it not? Dr. Shaw: At the moment she is on 40 mg temazepam at night. Dr. Davies:” Would she not perhaps be better stopping or tailing off temazepam rather than tailing off haloperidol? Dr. Shaw: I am sure she would. Dr. Davies: Certainly, from an addiction point of view she would be better off with small doses of haloperidol. Dr. Peter Jenkins: I think the issue of addiction with benzodiazepines in cases like this is very controversial. When you give people morphine after surgery, unless you are really liberal, they do not get addicted, and you have the same sort of thing here. Dr. Davies: You have a defined end point when you give morphine for surgery. Where is your projected end point for benzodiazepines? Dr. Peter Jenkins: Clearly, an end point you need to achieve here is resolution of the medical problem, also resolution of the family and social problems that accompany it. Dr. Richard Jenkins: You said this was not familial, but then the youngest daughter has abnormalities similar to those of her mother, and psychiatric problems. Dr. Shaw: We felt that the patient’s presentation was not typical of previously described familial HPPs and were surprised by the daughter’s abnormal in vitro results. The daughter has no symptoms of HPP and has not shown hyperkalemia. Dr. Peter Jenkins: Are you saying that because the youngest daughter shows the same test-tube binding, her overdoses are directly related to that? It strikes me we have quite a good explanation. The first overdose was when this lady had Evans syndrome, when she was severely ill, and possibly when she was operated on, and the second overdose was in the context of this again very frightening, threatening, paralysis. You do not need to have a biologic explanation for the daughter’s overQegistrar in Psychiatry, University of Wales College of Medicine. “Senior Registrar in Psychiatry, University of Wales College of Medicine.

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doses. There is plenty of social and psychologic stress to account for that. Dr. Shaw: Amiodarone is widely used as an effective antiarrhythmic. There are one or two reports in the literature of amiodarone psychosis. There have been three reports of paranoid reactions possibly related to amiodarone therapy. One of them was a psychosis that took the form of an exacerbation of a preexisting psychiatric condition [9]. There are a few reports of hallucinations, and some of personality problems, possibly preceding hypothyroidism [lo], but I do not know whether you can count Mrs. H. as having a premorbid state. Dr. Peter Jenkins: The issue of her premorbid state is one that is very complicated. Clearly, she has a predisposition towards psychiatric illness; she has a family history with obsessive-compulsive disorder and some other unknown problems. Her father was alleged to be an alcoholic and violent, and deserted her mother; her youngest child, who has the same trait, has taken overdoses at the ages of 10 and 6. The patient herself has had episodes of agoraphobia and quite severe anxiety that required treatment with benzodiazepines. This started after the birth of this youngest child and, obviously, such a picture makes one feel that an affective disorder might be present. At the time she was seen as an emergency she clearly had all the Schneiderian first-rank symptoms and a fullblown paranoid psychotic picture, which she narrates quite clearly. There are some who feel that this is pathognomonic of schizophrenia, but such features can also be present in organic psychosis [ll]. In DSM-III terms, a diagnosis of organic delusional syndrome secondary to amiodarone appears appropriate. Dr. Shaw: We also concluded that the psychosis could be attributed to amiodarone therapy and was unrelated to the HPP.

References Weatherall DJ: Autoimmune haemolytic anemia. In Weatherall DJ, Ledingham JGC, Warrel DA (eds), Oxford Textbook of Medicine, vol. III. Oxford, Oxford University Press, 1987, pp 19, 144-146 Walton J: Hyperkalaemia periodic paralysis. In Weatherall DJ, Leadingham JGC, Warrel DA (eds), Oxford Textbook of Medicine, vol. II. Oxford, Oxford University Press, 1987, p 22 Lishman WA: Systemic lupus: Involvement of nervous system. In Organic Psychiatry. Oxford, Blackwell Scientific Publications, 1988, pp 516-520

Psychosis with Hyperkalemic Paralysis

4. Fawcett JA, Bunney WE: Pituitary adrenal function and depression. Arch Gen Psychiatry 16:517-535, 1967 5. Gelenberg AJ: The catatonic syndrome. Lancet 13391341, 1976 6. Surman OS: Haemodialysis and renal transplantation. In Hackett TP, Cassera NH (eds), Handbook of General Hospital Psychiatry. Littleton PSG Publishing Co. Inc., 1987, pp 380-403 7. Orbach I: Assessment of suicidal behaviour in young children: Case demonstrations. In Diekstra RFW, Hawton K (eds), Suicide in Adolscence. Dordecht, Martiners Nijhoff Publishers, 1987

8. Hill P: Suicide in children. In Hill I’, Murray EM, Thaley A (eds), Essentials of Postgraduate Psychiatry. New York, Grune & Stratton, 1979, p 116 9. Middlefell CA: Amiodarone paranoid reactions. Personal Communication, Sanofi (UK) Ltd., 1987 10. Coumel I’, Fidelle J: Amiodarone in the treatment of cardiac arrythmias in children : One hundred-andthirty-five cases. Am Heart J 100(6)1063-1069, 1980 11. Cummings J: Organic delusions: Phenomenology and anatomic correlation. Br J Psychiatry 146:1&l198, 1985

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