Case Report

PRIMARY HYPERALDOSTERONISM STARTED BY

HYPOKALEMIC COMA - CASE REPORT

L. Dumitrache1, D. Bartos1,2, M. Beuran1,2, S. Ghiorghe1, C. Tarziu1, E. Badila1,2

1Emergency Hospital Bucharest, Romania

2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

Abstract
Primary hyperaldosteronism is the cause of approximately 0.05 to 2.2% of all
unselected cases of hypertension. It was first described in 1955 by Conn in conjunction with
aldosterone-producing adrenal adenoma, which is the most frequent aetiology, in 65% of
cases. Clinical features are usually non-specific and result from potassium depletion. We
report here the case of a 54-year-old woman who was admitted to the emergency department
due to coma (Glasgow score 6). The presence of severe potassium depletion (1.2 mmol/L)
and metabolic alkalosis (PH=7.76, base excess>30 mmol/L) in a hypertensive patient
determined the clinicians to search for a secondary cause of hypertension. This was
confirmed by localizing on computer tomography a right adrenal adenoma of 31-mm
diameter and on endocrine measurements that showed mineralocorticoid excess (plasma
aldosterone=764 pg/mL;N=14-193). Clinical evolution was slowly favourable after
restoring the electrolyte balance, with increasing of serum K up to 3.05 mmol/L. The patient
became asymptomatic in 3 weeks and underwent laparoscopic right adrenalectomy. The
patient had a good postoperatory evolution. Two weeks after laparoscopic right
adrenalectomy, blood pressure normalized after the discontinuation of the antihypertension
treatment and the aldosterone measurement was normal (102 pg/mL).

Key words: Conn disease, primary aldosteronism, secondary hypertension.

INTRODUCTION

Secondary hypertension is present in approximately 10% of hypertensive patients.

In addition, hypertension refractory to antihypertensive treatment may prompt the
clinician to screen (search) for secondary causes (1). One of the causes of secondary
hypertension is primary mineralocorticoid excess state, characterized by suppressed
plasmatic renin activity (PRA) and hypokalemia. It includes primary aldosteronism,
congenital adrenal hyperplasia (17-α-hydroxylase deficiency and 11-β-hydroxylase

*Correspondence to: Lacramioara Dumitrache MD, Emergency Hospital Bucharest, 8, Calea

Floreasca Sector 1, Bucahrest Romania, Phone: (+4021) 599.23.00 Email: lulu74ro@yahoo.com.

Acta Endocrinologica (Buc), vol. V, no. 2, p. 251 - 258, 2009

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deficiency) and increased mineralocorticoid action (apparent mineralocorticoid excess-

congenital; licorice ingestion, ectopic corticotrophin production; Liddle´s syndrome).
The clinical symptoms of primary aldosteronism are nonspecific and result
from potassium depletion. Most frequently they are neuromuscular symptoms
(weakness, periodic paralysis, cramps or tetany), fatigue and paresthesias. Polyuria
and nocturia can result from a hypokalemia-induced impairment of renal
concentration and defect mechanisms.
The arterial hypertension associated with hypokalemia hides in several cases an
etiology which should be carefully searched, excluding all the situations mentioned
before. We consider that the investigation of adrenal function, which usually is not made
in the clinics of internal medicine or cardiology, it is an important stage for the diagnosis
and the cure of some cases of secondary hypertension.
Although hypokalemic coma is very rare, it is important as a cause of
consiousness disorder. We present here the case of a patient whose first
manifestation of mineralocorticoid excess was hypokalemic coma.

CASE REPORT

Patient ME, a 54-year-old woman, from Bucharest, non-smoker, whithout

toxic environment history, was admitted to the emergency room due to coma. The
patient’s family was informed about the medical procedures and gave the informed,
written consent.
The family medical history includes a sister with an adrenal tumour treated by
surgery. Unfortunately, we did not have information about the functional state of
the tumour. The patient has been known with hypertension with highest values up
to 200/100 mmHg in the last two years (since 52 years old). Currently, she is treated
with betablockers and enzyme conversion inhibitors, but the values of blood
pressure were not wellcontrolled. She also has type 2 diabetes mellitus, chronically
treated with oral anti-diabetic drugs.
During the morning of admission day, the patient presented sleepy state, that got
progressively worse up to the loss of consciousness, with hypersalivation, discrete
muscular contractions of hands and deterioration of the general status. Prior to the loss of
consciousness, the patient did not present other symptoms. According to family
statements, the patient did not manifest previously vomiting, diarrhea, laxative abuse and
has not been in treatment with betaagonists or diuretics lately.
The general physical exam showed a deteriorated general state, pallor of skin,
oral and peripheral cyanosis, a pulse rate of 90 beats/minute with arrhythmia, blood
pressure of 170/80 mmHg, polyuria of 3100 mL (measurement started from the
admission in the emergency room by urinary catheterisation and recorded for 24 hours,
without diuretics); the neurological examination established: Glasgow 6 (Eye=2,
Verbal=1, Motor response=3) coma . The exam did not identify a tetraplegic syndrome.
The patient also showed imminence of respiratory arrest requiring intubation and

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mechanical ventilation in the Emergency Reception Unit. The patient was then admitted
in the Intensive Care Unit, where she got stabilized during the next 48 hours, which
allowed detubation and transfer in the Internal Medicine Department.
Laboratory tests showed severe hypokalemia=1.2 mmol/L (N=3.6-5), with
normal values of blood sodium =140 mmol/L (N=137-145), slightly raised
glycemia values=115-133 mg/dL (N=60-100), normal calcemia=8.9 mg/dL
(N=8.5-10.5) and normal calciuria=3.5 mmoL/24h (N=2.5-7.5); urinary electrolytes
measurement showed high levels of K =112.8 mmol/L (N=20-60) with high values
of urinary Na=438 mmol/L (N=137-145). Acido-basic balance revealed severe
metabolic alkalosis with pH=7.79 (N=7.35-7.45) and base excess >30 mmol/L
(N=± 2), HCO3 std=46.8 mmol/L (N=19-24), paO2=147.2 mmHg (N=75-100), pa
CO2=49.6 mmHg (N=35-45).
The renal function showed normal values of blood urea and creatinine: urea=30.5
mg/dL (N=15-36), creatinine=0.74 mg/dL (N=0.7-1.2). Proteinuria was normal=60
mg/24h (N<120).
The electrocardiogram pattern showed ventricular tachycardia (recorded only on
the monitor screen). The sinusal rhythm was re-established by external electrical shock
and after that the patient received infusion with xiline 1% for a short period of time.
Afterwards ventricular bigeminism occurred, modifications of end (-diastolic) phase in
all derivations and flattening of T wave (Fig.1).
Considering this clinical-paraclinical context, a cranial computed tomography
scanning examination was performed, which had a normal aspect, while the abdomino -
pelvic CT scan showed a right adrenal adenoma of 31-mm diameter (Fig.2 ). The other
adrenal gland was normal on CT scan.
A presumptive diagnosis of primary aldosteronism was made and because the
measurement of plasmatic renine activity was not available at the moment, only plasma
aldosterone was measured, showing a very high level=764 pg/mL (N=14-193). The
dynamic tests for detecting autonomous hypersecretion of aldosterone (captopril test and

Figure1. ECG revealing changes of hypopotassemia (flattening of T wave and modifications

of end-phase in all derivations).

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Figure 2. CT image: right adrenal adenoma (arrow)

with hypodensity suggesting tumor necrosis.
acute saline loading) were not performed due to the aggravation of the clinical status. The
differential diagnosis with other possible causes of hypokalemic coma took into account
potential potassium gastrointestinal losses, but the patient’s history did not reveal any
vomiting, diarrhea, laxative, abuse or tube drainage, hypothermia, previous betaagonists,
diuretics or insulin use.
As PRA (renin activity) measurement was not available, the differential
diagnosis with pseudo-Bartter syndrome relies on its most probable childhood onset
and on the normal values of blood pressure associated with the pseudo-Bartter
syndrome. The patient did not have hypercalciuria either.
We excluded in this case Liddle ‘s syndrome (pseudohyperaldosteronism), an
autosomal dominant disorder in which affected subjects present with hypertension
and suppressed PRA, hypokalemia but aldosterone levels are low. The hypokalemic
state cannot be corrected by administration of the antimineralocorticoid
spironolactone; this disorder is caused by mutations in the subunits of the renal
sodium epithelial channel (2,3).
The differential diagnosis with the hypertensive forms of congenital adrenal
hyperplasia associated with hypokalemia comprises 11-β-hydroxylase deficiency
(CYP 11 B) and 17-α-hydroxylase deficiency (CYP17). The elevated blood
pressure and hypokalemia in both syndromes result from elevated levels of DOC, a
potent mineralocorticoid; excessive sodium retention and hypertension result and
lead to suppression of PRA, but the levels of aldosterone are low, different from
Conn’s syndrome.
For an accurate differential diagnosis other tests were run to investigate the
secretion of the adrenal gland. We excluded the Cushing syndrome considering the
normal plasma cortisol value 8 a.m.=10.07 µg/dL (N=10-20), which, after running
the test with Dexamethasone 1 mg over night, was suppressed to 0.8 µg/dL (N<5).
Plasma and urinary methanephrines and normethanephrines were at normal levels:
plasma methanephrines =17 pg/mL (N<45); plasma normethanephrines = 65 pg/mL
(N<90); urinary methanephrines=200 µg/24 hours (N=<350); urinary
normethanephrines=430 µg/24 hours (N<600).

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The initial objective of treatment was restoring the electrolyte balance. Therefore,
we initiated treatment with KCl solutions, Spironolactone 100 mg/day and acid
Asparticum 540 mg/day. The evolution has been slowly favourable, with increasing of
serum K up to 3.05 mmol/L. The patient became asymptomatic in 3 weeks.
The surgical cure was preceded by a two-week treatment with calcium
blockers (Amilodipinum 10 mg/day), Spironolactone 150 mg/day and potassium
supplements. Before surgery, serum K was 3.97 mmol/L. Laparoscopic right
adrenalectomy was performed with a favourable evolution after surgery.
The histopathological pathology examination confirmed the presence of
adrenal adenoma of glomerular zone, looking like a tumoural proliferation limited
by conjunctive capsule, comprising especially spongiocitary cells and compact cells
in small proportion, with cell areas presenting pleyomorphism; the adjacent
fragment of adrenal gland had no changes. The immunochemistry of the tumour
was not performed.
Two weeks after surgery, serum and urinary values of sodium and potassium
came back to normal (K=4.5 mmol/L, Na=142 mmol/L, urinary K=43 mmol/L),
blood pressure normalized also after the discontinuation of the antihypertension
treatment. Equally, the aldosteron measurement was normal (102 pg/mL) as well as
plasma cortisol (16.3 µg/dL).

DISCUSSION

This case may be considered an unexpectedly variant given the clinical onset,
with sudden metabolic coma, that can often have a complex aetiology. We also note
the absence of transient troubles of hypoaldosteronism who can persist sometimes
up to 1-2 months after surgery.
The clinical symptoms of primary aldosteronism are non-specific and result
from potassium depletion. Most frequently they are neuromuscular symptoms
(weakness, temporary paralysis, cramps or tetany), fatigue, paresthesias, polyuria.
We consider the present case a particular one due to the sudden onset, with coma,
an onset rarely noted in adrenal tumours and more frequent in hypophysis pituitary
tumours. As for the mechanisms leading to coma, we can consider 3 cumulated
factors: severe hypokalemia, methabolicmetabolic alkalosis and the cerebral
hypoperfusion, along with the ventricular arrhythmia. Only a few cases of
consciousness disorder following hypokalemia have been reported (4, 5). The
pathophysiological mechanisms of the hypokalemic coma are unclear. Changes in
transmembrane potential or inhibition of intracellular enzymes following
intracellular potassium depletion have been suggested as mechanisms (5).
In the medical literature we found a single reported case of primary aldosteronism
with hypopotassemic coma (6). It is a female patient who had a hypopotassemic coma
four years after she was diagnosed with the Conn syndrome. As she did not undergo
surgery and before being readmitted she had been complaining of severe headache,

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muscle weakness and fatigue, paresthesia in both hands and nocturnal polyuria. During
the last five days she had been treated with hydrochlorothiazide, which is
considered by the authors as the factor that caused the hypopotassemic coma. As
many as 50% of patients with primary aldosteronism may have proteinuria. Renal
failure may occur in as many as 15% of patients (1). These disturbances did not
occur in the case presented by us.
The severe hypokalemia can be associated, like in our case, with ventricular
tachycardia which has the risk to degenerate into ventricular fibrillation, a malignant
ventricular arrhythmia, that’s why it should be rapidly treated. The treatment should be
made urgently with synchronized external electric shock (200-400 J), concomitantly
restoring the electrolyte balance.
The preventive treatment can use antiarrhythmic drugs like Amiodarone,
Mexiletine, Propaphenone or betablockers. In our case, the antiarrhythmic treatment was
not necessary long time after attack because the patient did not repeat arrhythmia after the
re-establishment of the normal level of potassium.
The normal sodium levels in the presence of severe hypokalemia can be explained
by the escape of aldosterone’s effect which triggers a degree of spontaneous diuresis and
increased levels of urinary Na. This situation is initiated by the increase of volemia and
the mechanisms involved are the increase of the atrial natriuretic peptide secretion as well
as the increase of the Na renal secretion by an increased renal pressure infusion under
systemic hypertension conditions. Usually, hypertension associated with primary
aldosteronism gets medium or severe levels, with values of 184±8 with 112±6 mmHg
(1). Some patients can have malignant hypertension while others have normal or
only mildly elevated blood pressure. Individuals with adrenal adenoma-producing
aldosterone tend to have higher blood pressures than those with idiopathic
hyperaldosteronism. They may be refractory to conventional antihypertensive
agents and may experience severe hypokalemia after taking potassium wasting
diuretics such as hydrochlorothiazide (7).
Unilateral adrenalectomy in patients with aldosterone-producing adenomas or
unilateral hyperplasia induces a marked reduction in aldosterone secretion and correction
of the hypokalemia in almost all patients (7-9). Hypertension is improved in all and is
cured in approximately 35 to 60 percent of patients (7,8,10,11). In our patient’s case,
blood pressure has been normalized in 2 weeks after surgery.
Usually, laparoscopic adrenalectomy is preferable because it is associated with
shorter hospital stays and fewer complications (12-16).
Postoperative management after unilateral adrenalectomy should include the
following (17,18):
- Plasma aldosterone should be measured the day after surgery to assess for cure;
- Potassium supplements and spironolactone should be discontinued, and if
possibly, antihypertensive therapy should be decreased;
- Patients should be monitored closely for hyperkalemia which may result
from transient hypoaldosteronism; serum potassium should be measured during the
hospitalization, and as an outpatient, once weekly for four weeks.

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The situations in which the hypertension is associated with severe

hypokalemia should be very carefully approached, because in several cases, the
aetiology can be primary hyperaldosteronism, Cushing’s syndrome, adrenal
hyperplasia with enzyme defects (11-β hydroxylase or 17-α hydroxylase
deficiency), Liddle’s syndrome.
Resistant hypertension is defined as blood pressure that remains uncontrolled
despite using at least three antihypertensive medications in effective doses, ideally
including a diuretic (7). Hyperaldosteronism is now recognized as the most common
secondary cause and all patients with resistant hypertension should be screened with a
plasma aldosterone-renin ratio even if the serum potassium level is normal.
The screening tests concern all patients having hypertension and spontaneous
or easily triggered hypokalemia, patients with treatment-resistant hypertension,
those patients with early onset hypertension (under the age of 40), patients with
adrenal incidentaloma or those who have a family history of hypertension or stroke.
The screening tests are represented by aldosterone-renin ratio (aldosterone/PRA);
values over 30 indicating primary aldosteronism, while values over 50 certify the
primary aldosteronism diagnosis (19-21). A potential limitation would be the
inability to determine the PRA in the early diagnosis phase.
In conclusion, severe, life threatening hypokalemia can be associated with
metabolic coma and should immediately point to possible primary
hyperaldosteronism, in the absence of another obvious cause.

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