Conn’s Syndrome: An Unusual Cause of Periodic Paralysis

Primary hyperaldosteronism, also known as Conn’s syndrome, is characterized by an independent and excessive aldosterone production in the adrenal cortex, causing hypernatremia, arterial hypertension, and, in some cases, potentially severe hypokalemia can occur. We report a case of a 45-year-old Caucasian woman, with a history of obesity and hypertension, who presented to the emergency room with a four-week evolution history of myalgia and ascending muscle weakness eventually resulting in tetraparesis. The initial blood analysis showed severe hypokalemia (1.5 mmol/L). Further laboratory studies revealed an elevated plasma aldosterone level with low renin activity, and thyroid function tests were consistent with mild primary hyperthyroidism. CT scan showed a nodular lesion in the left adrenal gland. A saline suppression test confirmed that aldosterone secretion and renin activity were not suppressed. Regression of tetraparesis was noted with vigorous potassium supplementation. A laparoscopic left adrenalectomy was performed, with consequent normalization of hypokalemia, without the need for supplementation. Periodic paralysis (PP) are a rare group of neuromuscular diseases that occur due to the affection of the ion channels of the skeletal muscle. Most cases are hereditary; nonetheless, secondary causes of PP have been reported in the literature. This case illustrates an unusual and severe presentation of primary hyperaldosteronism manifested by PP. The concomitant changes in thyroid function raised the possibility that we are facing the clinical influence of another rare entity: thyrotoxic hypokalemic PP. However, the resolution of hypokalemia after the removal of adrenal adenoma supported the major contribution of hyperaldosteronism.


Introduction
Primary hyperaldosteronism, also known as Conn's syndrome, is characterized by an independent and excessive aldosterone production in the adrenal cortex, mostly derived from an aldosterone-producing adenoma or bilateral adrenal hyperplasia. The clinical features of primary hyperaldosteronism are mainly related to aldosterone-induced renal sodium reabsorption, causing hypernatremia, arterial hypertension, and, in some cases, a hypervolemic state. In addition, potentially severe and refractory hypokalemia can occur due to increased renal potassium excretion.

Case Presentation
A 45-year-old Caucasian woman presented to the emergency room with a four-week evolution history of myalgia and ascending muscle weakness, first noticed in the lower limbs, and then progressed to upper limbs and cervical musculature. On the day of admission, there was rapid evolution to disabling tetraparesia. She reported similar but less severe episodes of muscle weakness in the last few months, with spontaneous resolution. She also noted, in the previous three months, involuntary weight loss (10 kg), polydipsia, polyuria, and nocturia (without fever, respiratory or gastrointestinal symptoms).
The patient had a history of obesity and hypertension of young age onset (20 years) with an incomplete investigation for secondary causes because she missed follow-up appointments, but tightly controlled with an association of perindopril/amlodipine. There were no new medications, vaccines, supplements, or known toxic exposure. There were no recent travels or any relevant epidemiological contact. A high carbohydrate meal was consumed the night before the admission.
On physical examination, she was hemodynamically stable. The neurologic evaluation revealed a general diminished muscular strength with the inability to exert force against gravity. Pain, tactile, and protopathic sensitivity were intact. Deep tendon reflexes were attenuated but symmetrical in all limbs. A vesical globe was noted. A 15 mm central, well-defined, painless thyroid nodule was palpable.

EKG, electrocardiogram
Despite an initial period of intense potassium supplementation (in the first four hours, by central venous perfusion, with ~ 40 mEq/h), followed by maintenance of potassium infusion ~10 mEq/h, together with magnesium sulfate, for at least five days, we witnessed a very refractory ionic correction. Paradoxically, muscle strength fully recovered, with the patient being asymptomatic and able to walk on the second day of supplementation, although undercorrected potassium levels. Muscle enzyme levels decreased progressively and became normal with days. She never developed dysrhythmias or cardiovascular symptoms.
Further laboratory studies revealed an elevated plasma aldosterone level with renin activity levels being inappropriately reduced ( Table 1). Thyroid function tests were consistent with mild primary hyperthyroidism. They also revealed slightly increased anti-diuretic hormone levels, probably compensatory as serum and urinary osmolality were preserved. The remaining endocrinological study was normal.   (Figures 2-3). The right adrenal gland was normal.  Thyroid ultrasound revealed small but multiple nodules (TI-RADS 3), compatible with toxic nodular goiter after scintigraphy was performed. Anti-thyroid antibodies (anti-thyroid peroxidase -TPOAb and TSH receptor antibodies -TrAb) were negative. To exclude other causes of muscle weakness, spinal CT, cranial MRI and electromyography were performed, showing no alterations. The combination of hypertension, hypokalemia, abnormal aldosterone levels, and the presence of an adrenal mass raised the clinical suspicion of Conn's syndrome. A saline suppression test corroborated the diagnosis as aldosterone secretion and renin activity were not suppressed after a four-hour saline infusion ( Table 2).
Treatment with spironolactone was initiated with a very good response, allowing for a progressive decrease in the daily supplemental potassium intake. After normalization of potassium levels, a laparoscopic left adrenalectomy was performed, with consequent normalization of kalemia without the need for supplementation. Histological analysis confirmed an adenoma with free surgical margins ( Figure 4).

FIGURE 4: Mass removed through laparoscopic left adrenalectomy.
In the follow-up, three months after the surgery and without potassium supplementation or spironolactone, she was asymptomatic, without strength deficits, and with a corrected ionogram. It was possible to discontinue antihypertensive drugs, with good blood pressure control.

Discussion
Periodic paralysis (PP) are a rare group of neuromuscular diseases that occur due to the affection of the ion channels of the skeletal muscle. Usually, they are differentiated according to blood potassium levels: hypokalemic or hyperkalemic PP [1].
They are manifested by the sudden and transient appearance of muscle weakness, usually proximal and symmetrical, starting with the lower limbs and with proximal progression. Classically, acute episodes may be preceded by a prodromal period consisting of myalgias and muscle spasms, which may be precipitated by the ingestion of carbohydrate-rich meals or after vigorous physical exercise. Other less common precipitants include trauma, exposure to cold, infection, menstruation, and the use of drugs such as diuretics, insulin, or corticosteroids. The duration of episodes may last a few minutes or several days. Most resolve spontaneously, however, severe potassium depletion may culminate in tetraplegia and death from respiratory muscle failure and/or fatal arrhythmias [1][2]. PP can also affect other systems, such as cardiovascular and gastrointestinal.