Case Sharing l Primary aldosteronism: 1 month after operation of right primary aldehyde adenoma-hypotension shock-high potassium and low sodium-pleural effusion-hypoxic pulse

The 34-bed old man was finally discharged from the hospital smoothly.
Dwarf oil is good~.

I first stayed in the ICU for 7 days, then transferred to the emergency room for 7 days, and finally stayed in the general ward for another 7 days.
The inpatient diagnosis and treatment process for more than 3 weeks was a bit tortuous.

We know that patients with unilateral adrenal cortisol adenomas need about 18 months of glucocorticoid replacement, waiting for the suppressed adrenal cortex tracts to resume the function of secreting cortisol, otherwise cortisol deficiency will appear.
It will be more obvious in the state of excitement.

A few days ago, I also encountered a patient with Cushing’s syndrome 2 weeks after unilateral adrenal surgery in the urology department.
The main complaint was obvious fatigue and anorexia.

It turned out that the surgeon did not give glucocorticoid replacement after discharge, and did not instruct the endocrinology department to follow up.
The patient was in a state of primary adrenal insufficiency, which led to the above-mentioned clinical symptoms.

Outpatient review of low cortisol and high ACTH, and then replaced with physiological dose of prednisone and explained the follow-up matters.

In our impression, primary aldehyde is different from Cushing.
It seems that few patients with unilateral primary aldehyde adenoma need mineralocorticoid replacement after surgery, and none of the previous primary aldehyde patients in our department need replacement.

However, the course of this old man’s disease was beyond our expectation.
The diagnosis and treatment process is a bit complicated, not as expected, such as refractory hypotension shock, acute hyperkalemia and hyponatremia, acute renal insufficiency, hypoxemia/pulse oxygen, continuous pleural effusion, etc.
smoothly.

The diagnosis and treatment of this case and the clinical thinking process are shared as follows.

Case data General medical history: WSN, 5398014, male, 76 years old, 2020.
11.
1-23 Chief complaint: diarrhea with vomiting for 1 day, chest discomfort for 40 minutes.
Medical history: the patient took "catharsis-relieving capsule" for constipation 1 day ago.
Diarrhea occurred 5 times after 4 capsules, and the stool was watery yellow, accompanied by vomiting 2 times of stomach contents. 40 minutes ago, chest discomfort and depression occurred.
The specific nature cannot be described.
The family members were rushed to our hospital.
The blood pressure was 64/42mmHg and the heart rate was 35 beats/min in the emergency department.
After administration of atropine, isoproterenol, and balance solution, the cause of shock was assumed.
"Pending investigation" is admitted to ICU according to cardiology patients.

During the course of the disease, the patient was mentally clear, mentally lethargic, without fever, cough and asthma, chest pain, abdominal pain, abdominal distension, hematemesis, and melena.

Past history: "Hypertension" for 10 years, usually taking "betaloc, amlodipine, enalapril" to control blood pressure in general, "laparoscopic right adrenal tumor resection in the outside hospital more than one month ago "The blood pressure was normal after the operation.

Denies the history of "diabetes, coronary heart disease, lung disease".

Physical examination: BP65/41mmHg, medium size, clear mind, lethargy, Cushing's signs (-), bilateral pupils are equal in diameter, 3.
5mm in diameter, slow to light reflection, clear breath sounds in both lungs, undershot rales, The heart rate is 49 beats/min, the rhythm is uniform, the abdomen is flat and soft, there is no edema in the lower limbs, the muscle tone of the limbs is normal, and the pathological signs (-).

Auxiliary examination: heart rate of 35 beats per minute as shown in electrocardiogram, sick sinus syndrome.

Preliminary diagnosis: shock to be investigated: cardiogenic? Insufficient blood volume? After diagnosis and treatment of sick sinus syndrome, the condition is critically ill, monitoring, oxygen inhalation, deep subclavian catheterization, dopamine combined with norepinephrine and isoproterenol continuous pumping, rapid volume expansion, maintaining electrolyte balance, and maintaining blood pressure at 90 /50mmHg, CVP3-4cmH2O, and perfect auxiliary inspection at the same time.

On the day of admission (2020-11-1), abdominal ultrasound: gallbladder wall edema, abdominal effusion, right upper abdomen and 23mm liquid dark area, lower abdomen and 31mm liquid dark area, liver, pancreas, spleen and kidneys and ureters were normal.

Thoracic ultrasound: bilateral pleural effusion, about 33mm deep on the right side and 32mm deep on the left side.

Cardiac ultrasound: LVEF 56%, the size of each cavity is normal, the motion of each segment of the ventricular wall is good in the resting state, the left ventricular diastolic function is decreased, and the mitral valve and aortic valve insufficiency are mild.

Intravenous ultrasound: there were no abnormalities in the deep veins, hepatic veins and inferior vena cava of both lower limbs.

Our department of clinical thinking was invited for consultation.
The patient’s family did not carry previous case data, the description of the condition was unclear, and the nature of the adrenal mass was unknown.

The patient suffered from severe clinical symptoms such as shock, high potassium and low sodium for more than one month after unilateral adrenal surgery, diarrhea, vomiting, and other serious clinical symptoms.
Considering the possibility of adrenal crisis is high.

It is speculated that the patient may have undergone unilateral adenoma resection due to "adrenal cortisol adenoma" (although the patient has no typical Cushing signs), but he did not receive physiological dose glucocorticoid replacement after surgery, stress (diarrhea) , Vomiting), an adrenal crisis occurs.

Figure 1 Normal negative feedback regulation of cortisol and aldosterone secretion Note: (A) Hypothalamus-pituitary-adrenal axis (HPA axis).

Corticotropin (ACTH) is secreted by the anterior pituitary gland and is affected by the two main secretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin, and other factors including cytokines also play a role .

The secretion of corticotropin releasing hormone (CRH) is regulated by the inherent circadian rhythm and additional stressors acting through the hypothalamus.

The secretion of corticotropin releasing hormone (CRH) and corticotropin (ACTH) is inhibited by cortisol, which emphasizes the importance of negative feedback control.

(B) Renin-Angiotensin-Aldosterone System (RAAS).

Renin is secreted by cells around the glomerulus and depends on the blood pressure of the renal artery.

Renin converts angiotensinogen to angiotensin I, which is converted to angiotensin II in the lungs by angiotensin-converting enzyme (ACE).

Angiotensin stimulates the synthesis of adrenal aldosterone, and the extracellular part of potassium (ECF) has an important direct inhibitory effect on the secretion of aldosterone.

AVP (Antidiuretic Hormone); ANP (Atrial Natriuretic Peptide).

Note: The amount of aldosterone produced is determined by the input of each cycle.

ACE, angiotensin converting enzyme; Na+, sodium ion.

Figure 2 Renin-angiotensin-aldosterone (RAA) and potassium-aldosterone negative feedback loops.
From these charts, we know that the HPA axis (hypothalamus-pituitary-adrenal axis) is relatively simple, and the main line of this axis—CRH-ACTH- F—An abnormality in any one of the three will significantly affect the function of the adrenal cortex, and if there is a chronic long-term effect, it will take a longer time for the HPA axis to return to normal.

Similar to humans, the more supporting factors such as self, family, friendship, and society, the more stable the individual, the stronger the individual's ability to resist blows/recovery, the less likely it is to collapse, and vice versa.

After successful surgery, patients with Cushing’s syndrome need glucocorticoid replacement therapy until the HPA axis returns to normal.
This recovery process is usually about 6-12 months after the ACTH tumor is removed, and after unilateral adrenal (lesion) resection About 18 months, the HPA axis recovery time of adrenal cortisol tumors is longer than that of pituitary ACTH tumors overall.

In addition, in patients treated with long-term exogenous glucocorticoids (such as connective tissue diseases, asthma), it takes 6-9 months for the HPA axis to be released, the secretion of CRH gradually returns to normal within a few weeks, and ACTH within a few weeks The internal level began to increase, and the level was higher than normal until the adrenal steroid synthesis was restored.
This process is similar to that after adrenal cortisoloma.

If these patients are not given glucocorticoid replacement, clinical manifestations of adrenal insufficiency will occur, such as fatigue, anorexia, nausea and vomiting, weight loss, muscle and joint pain, and even adrenal crisis under stress.

The renin-angiotensin-aldosterone system (RAAS) is different.
There are many regulating factors for aldosterone production, including circulating blood volume, blood pressure, catecholamines, potassium, and sodium.
Its "support system" is much stronger than the HPA axis.

This results in the excessive aldosterone secreted by primary aldosterone adenomas having little effect on the contralateral adrenal cortex globular zone.
Therefore, most patients with primary aldehydes do not need mineralocorticoid replacement after surgery, which is significantly different from those in patients with Cushing’s syndrome.
s difference.

Therefore, we considered that the patient had a unilateral adrenal cortisol adenoma during the initial consultation.
It is recommended to give hydrocortisone 50 mg intravenously twice a day, and blood samples for ACTH, F, aldosterone, and aldosterone were taken before intravenous infusion.
Renin. At present, the blood pressure is still unstable after pumping large doses of vasopressor.
It is expected that the blood pressure will rise rapidly after intravenous infusion of hydrocortisone, and the vasopressor will be quickly removed.

Unexpectedly after diagnosis and treatment, there was no significant change in blood pressure after intravenous infusion of hydrocortisone, and large doses of blood pressure drugs were still needed to barely maintain it.
The treatment response was different from cortisol deficiency.

Hormone measurement before the application of hydrocortisone showed that random cortisol was 723.
48 nmol/l, renin was as high as 297.
802 ng/l, and aldosterone was only 79.
991 ng/l.

All this suggests that the HPA axis seems to be intact, and the RAAS response is insufficient, and there is a significant lack of aldosterone, which means that the patient’s surgery was a unilateral adrenal aldosterone adenoma surgery rather than a cortisol adenoma, which was subsequently brought by the patient’s family from home The discharge record confirmed the speculation.

Random discharge records for ACTH, F, renin, and aldosterone determinations Note: The discharge records show that the patient was diagnosed with primary aldosteronism due to hypertension and hypokalemia before surgery.

To evaluate whether the HPA axis function is intact by clinical thinking, diagnostic tests are needed to determine.

Basal plasma cortisol and urinary free cortisol are often in the lower normal range, and cannot be used to determine and rule out the diagnosis of cortisol deficiency.

However, a baseline (non-stress) cortisol value> 400 nmol/l must indicate a good HPA axis.

In clinical practice, all patients suspected of adrenal insufficiency should undergo the ACTH stimulation test instead of waiting for the insensitive cortisol rhythm, except for patients with adrenal crisis, they should be given active treatment immediately, and the stimulation test can be repeated later.
do.

The standard dose ACTH excitation test (SST) is safe, accurate and reliable in the diagnosis of adrenal insufficiency.

A pharmacological dose of exogenous ACTH1-24 (250ug) is given for excitability test, which is equivalent to the biological activity of natural ACTH containing 39 amino acids.

Intravenous or intramuscular injection, the serum cortisol concentration was measured before injection and 30 and 60 minutes after injection.

The peak value of cortisol after excitement is greater than 500nmol/L (180ug/L) is defined as normal.

Insulin hypoglycemia stimulus test (ITT) is also an option.
Normal insulin (0.
10-0.
15U/kg) induces hypoglycemia after intravenous injection.
Serum cortisol concentration is measured every 30 minutes and monitored for at least 120 minutes.
Cortisol peak value> 500nmol /l is defined as normal.

However, it is worth complaining that although the ACTH test is relatively safe and easy to operate, it is difficult to obtain ACTH in the clinic, so the ACTH excitement test cannot be performed.
At the same time, patients suspected of adrenal hypofunction are in poor condition.
The current doctor-patient environment Under the circumstances, few doctors are willing to take the risk to do insulin hypoglycemia excitement test, so these two tests used to determine HPA axis function can not be carried out routinely.
It is really embarrassing in capitalization.
.
.
And during critical illness, many factors make The inspection of the HPA shaft becomes complicated.

Cortisol levels vary greatly in severe illness, and it is difficult to define an appropriate response.

In addition, the decrease in the amount of cortisol binding globulin (CBG) leads to an increase in the ratio of free/serum bound cortisol, and tests to evaluate HPA axis function such as insulin hypoglycemia excitement test are not suitable in critical conditions, therefore, research is limited to Cortisol basal level or ACTH excitement test.

Recent guidelines suggest that random cortisol below 400 nmol/l indicates cortisol deficiency, and if it exceeds 900 nmol/l, it is unlikely to occur in patients with impaired HPA axis function.

Patients with moderate cortisol levels should undergo the ACTH excitation test-in critically ill patients, a cortisol increase of less than 250 nmol/l is an independent predictor of death.

A multicenter randomized clinical trial of patients with septic shock showed that patients with a cortisol increase of less than 250 nmol/l had a significant improvement in mortality after glucocorticoid replacement therapy.

Therefore, it is recommended that patients with low basal cortisol levels or moderate cortisol levels in critical illnesses but with a small increase in the excitement test should be given glucocorticoid replacement therapy, and further examinations after the patient recovers to confirm that the HPA axis function returns to normal.

Therefore, although we already know that this patient is suffering from aldosterone deficiency after primary aldehyde surgery, and the cortisol is randomized to 723.
48 nmol/l, we still recommend to continue to use hydrocortisone 50 mg intravenously twice a day until the condition is stable.
One is to To supplement part of the cortisol deficiency that may exist in the critical state (random cortisol is not greater than 900nmol/l, SST or ITT cannot be performed), and the second is to simulate the boosting effect of some mineralocorticoids.

Some people will say that since the patient is clearly aldosterone deficiency, then it will be all right to supplement mineralocorticoids directly.

But imagine the fullness and reality of skinny-another point of complaint: the mineralocorticoid fludrocortisone is also difficult to buy on the market.

However, although fludrocortisone is not available, there is always a way to simulate the effects of fludrocortisone in some way.

Before that, let's first understand-apparent mineralocorticoid hyperplasia (AME).

Figure 3 Classification of apparent mineralocorticoid hyperplasia Figure 4 Cortisol-corticosterone shunt Note: compare the isoenzymes of 11β-hydroxysteroid dehydrogenase (11βHSD).

11βHSD2 is a β-dehydrogenase that specifically acts on classic aldosterone target tissues to remove cortisol from other non-selective mineralocorticoid receptors (such as the kidney).

Inactivated cortisol is also present in the placenta.

11βHSD1 is an absolute dominant β-dehydrogenase in the body.
It exists in many tissues and can increase the concentration of glucocorticoids in local cells, so that the relatively low-affinity glucocorticoid receptors remain sufficient for the glands.
Of exposure.

Apparent mineralocorticoid hyperplasia (AME) is the result of impaired activity of the microsomal enzyme 11βHSD2, which is usually inactivated by converting cortisol (hydrocortisone) into inactive 11-ketone compounds Cortisol in the kidneys.

Cortisone is an effective mineralocorticoid.
When the 11βHSD2 gene is defective or its activity is blocked, high levels of cortisone will accumulate in the kidney, which can freely bind to unprotected mineralocorticoid receptors, causing high Blood pressure and hypokalemia. The decrease of 11βHSD2 activity may be hereditary, or it may be secondary to the pharmacological inhibition of enzyme activity by glycyrrhizic acid metabolite, the active ingredient of licorice.

The congenital form is a rare autosomal recessive disease, and fewer than 50 patients have been found worldwide.

Congenital apparent mineralocorticoid excess usually occurs in children with hypertension, hypokalemia, low birth weight, stunted growth, polyuria and polydipsia, and stunted growth.

The apparent mineralocorticoid excess due to the intake of licorice is manifested as hypertension and hypokalemia, and the cause becomes obvious when the relevant medical history is obtained.

In addition, when the large amount of excessive secretion of cortisol related to Cushing syndrome caused by ectopic ACTH syndrome exceeds the effect of 11βHSD2, hypokalemic hypertension may be one of the results.

The clinical phenotypes of patients with significant mineralocorticoid excess due to congenital 11βHSD2 deficiency or inhibition include hypertension, hypokalemia, metabolic alkalosis, low renin, low aldosterone, and normal plasma cortisol levels.

In the 24-hour urine collection, the abnormal (high) ratio of cortisol to cortisone can be confirmed, which indicates a significant excess of mineralocorticoid.

The characteristic abnormal urinary cortisol-cortisone metabolite profile reflects a decrease in 11βHSD2 activity; the ratio of cortisol to cortisone is usually 10 times higher than normal.

Deoxycorticosterone (DOC) levels may also increase in severe ACTH-dependent Cushing’s syndrome and cause hypertension and hypokalemia in the disease.

Since there is no fludrocortisone, we can suppress the activity of 11βHSD2 by taking licorice substances, simulate acquired apparent mineralocorticoid hyperplasia, and correct the patient's hypotension, hyponatremia and hyperkalemia.

Note: Studies have shown that taking glycyrrhizic acid 100mg/d for 4 weeks, systolic blood pressure increased by 5.
6±7.
9mmHg for non-hypertensive people, 12.
4±5.
1mmHg for hypertensive people; diastolic blood pressure increased by 4.
2±5.
7mmHg for non-hypertensive people, and hypertensive people Increase 9.
1±4.
5mmHg.

Glycyrrhizic acid is the active ingredient in licorice, some chewing tobacco and confectionery foods.

The safe dosage of glycyrrhizic acid: 50-100mg/d for sensitive individuals, 400mg/d for the general population, and the safe dosage is only 10mg/d.

The compound licorice tablet contains 7.
3 mg of glycyrrhizic acid per tablet.
The recommended dosage in the instructions is 3-4 tablets per time for adults, 3 times a day, that is, the total daily dose of glycyrrhizic acid is 65.
7-87.
6 mg.
The dosage is quite large.
Long-term use may cause serious problems.
Side effects: Hypertension, hypokalemia, renal sodium retention, increased blood volume and RAAS inhibition (low renin, low aldosterone) and metabolic alkalosis-serum potassium usually recovers 1-4 weeks after stopping, blood pressure usually Recovered within 1 month after discontinuation, while RAAS recovered 4 months after discontinuation.

In this case, we are taking advantage of the side effects of glycyrrhizic acid, which turns negative energy into positive energy, improves blood pressure and blood volume, preserves sodium and reduces potassium.

He was given 4 tid of compound licorice tablets (equivalent to 116.
8 mg/d of glycyrrhizin), and the blood pressure gradually stabilized.
After 4 days, the intravenous pump booster was stopped.
At the same time, renal insufficiency, high potassium and low sodium were corrected.
Diagnosis and treatment continued in the emergency room of the ward.

After diagnosis and treatment, although the hypotension was corrected after the patient was transferred to the ward, there were still repeated hypoxemia/pulse oxygen, continuous pleural effusion, low protein, etc.
, and the patient was transferred to the general ward after the diagnosis and treatment for 1 week, and the condition was stable after another week Discharged.

There are some twists and turns in the middle process, so I won’t make a detailed list here.

Changes in various indicators Note: Renal function and electrolytes are gradually improved, low albumin, and arterial blood gas indicators fluctuate.

Changes in each index Note: changes in pleural effusion, albumin, blood oxygen/pulse oxygen, blood pressure and heart rate.

During the hospitalization, a large number of pleural effusions were repeated, and the puncture examination revealed that the leakage was related to factors such as low albumin and heart failure.

Repeated hypoxemia/pulse oxygenation may be related to factors such as pleural effusion, post shock, anemia, etc.

Chest CT (11-3) Chest CT (11-11) Abdomen (adrenal gland) CT discharge diagnosis of aldosterone deficiency right adrenal aldosterone adenoma postoperative hypotension shock hyponatremia with hyperkalemia acute renal insufficiency sick sinus node Syndrome discharge plan, high sodium diet, monitoring blood pressure, medication plan, 4 tablets of compound licorice tablets qid, 1 week later.
At the initial consultation, the patient was preconceived that the patient was adrenal cortical insufficiency caused by adrenal cortisol adenoma after surgery, but not Deep thinking.

Because even after the adrenal cortisol adenoma, the clinical symptoms of cortisol deficiency should be mainly manifested: fatigue, anorexia, nausea and vomiting, stomach pain, muscle and joint pain, hypoglycemia, etc.
, there should be no obvious manifestations of mineralocorticoid deficiency : Dizziness, halophilia, hypotension, dehydration, elevated blood creatinine, low sodium, high potassium.

The patient showed a typical mineralocorticoid deficiency and no Cushing's signs.
The medical history after the original aldehyde operation should be inferred at the first consultation.

We need to understand that although RAAS is more stable than the HPA axis and does not take longer to recover after surgery in patients with Cushing syndrome, we still need to be alert to the inhibitory effect of high aldosterone secretion on the contralateral adrenal cortex globular zone in patients with primary aldehydes.

In the first few weeks after surgery, since the contralateral adrenal gland inhibitory effect has not been relieved, sodium intake should be increased.
If there is obvious manifestation of hypoaldosteronemia, fludrocortisone needs to be temporarily taken as an alternative therapy.

In addition, in clinical diagnosis and treatment, one should not be too rigid.
A thorough understanding of the pathophysiological mechanism of the disease can transform some side effects/adverse reactions into positive diagnosis/treatment effects.

In addition to this patient, compound licorice tablets are also an option for patients who often have orthostatic hypotension and cannot be caused by it.

Of course, the side effects of licorice-based substances on RAAS require a deep understanding.

The author introduces Dr.
Hu Yichuan, an attending physician in the Department of Endocrinology, Shuyang Hospital Affiliated to Xuzhou Medical University, and a member of the Endocrinology Branch of the Suqian Medical Association.
He is good at diagnosis and treatment of diabetes, thyroid diseases, pituitary diseases, electrolyte disorders and other related diseases. The author introduces Dr.
Zhang Qianjin, director of the Department of Endocrinology, Shuyang Hospital Affiliated to Xuzhou Medical University, deputy chief physician, lecturer, and postgraduate student, deputy director of the Endocrinology Branch of the Suqian Medical Association, and deputy director of the Suqian Medical Association of Integrated Chinese and Western Medicine.
Especially difficult, rare/rare diseases keep a keen interest, personal public account "endocrine regulator".

References: [1] Shlomo Melmed, Richard J.
Auchus, Allison B.
Goldfine et al.
Williams Textbook of Endocrinology 14th Edition, 2019: 480-573.
[2] Francis S.
Greenspan and other original works, main translation by Guo Xiaohui.
Clinical Endocrinology 7th Edition.
People's Medical Publishing House, 2009:352-425.
[3] Sigurjonsdottir HA,Manhem K,Axelson M et al.
Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice.
[ J] .
J Hum Hypertens, 2003, 17: 125-31.
[4] Expert consensus on the diagnosis and treatment of primary aldosteronism (2020 edition)[J].
Chinese Journal of Endocrinology and Metabolism,2020,36(9):727 -736.
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