Primary adrenal insufficiency
Secondary adrenal insufficiency
Autoimmune disease
Pituitary surgery, pituitary/brain trauma
Adrenal infections and inflammation
Acute interruption of prolonged glucocorticoid therapy
After adrenalectomy
Adrenal hemorrhagic necrosis caused by meningococcal sepsis or coagulation disorders
Presentation of Acute Adrenal Insufficiency (Adrenal Crisis)
Adrenal crisis is attributable to mineralocorticoid deficiency. The clinical presentation is dominated by hypotension or hypotensive shock, caused by sodium and plasma volume depletion. The associated prostaglandin excess (prostacyclin) and decreased responsiveness to norepinephrine and angiotensin II may aggravate the circulatory collapse. This clinical presentation is often preceded by acute abdominal pain or symptoms attributable to the etiology of acute adrenal insufficiency (e.g., sepsis, pituitary or adrenal hemorrhage or necrosis, surgery, or trauma).
Atypical Presentations
A new case of adrenal insufficiency may present as excessive fatigue, malaise, weight loss, vomiting, orthostasis, abdominal pain, hyperpigmentation, or biochemical disturbances. Hypoglycemia, salt craving, malaise, seizures, and even coma may be the presenting symptoms. Severe hyponatremia or metabolic acidosis is associated with poor outcomes and fetal death, if not recognized and managed promptly.
Maternal and Fetal Morbidity and Mortality
Adrenal insufficiency recognized in the antenatal period and managed properly does not cause severe maternal morbidity. Unrecognized adrenal insufficiency in pregnancy manifests in puerperium at the time when there is disruption of transplacental transfer of cortisol from fetus to mother [26]. Gestational adrenal insufficiency has been associated with high rates of intrauterine growth restriction [35, 36] and fetal mortality.
Diagnosis of Acute Adrenal Insufficiency
One should be highly suspicious of adrenal crisis in case of unexplained hypotension, especially in high-risk patients (e.g., AIDS patients, patients with autoimmune disease, patients on prior glucocorticoid therapy). If acute adrenal insufficiency is suspected, simple diagnostic screening procedures should be used based on what is rapidly available. Immediate therapeutic intervention is required even before the diagnosis is formally confirmed. The following laboratory investigations should be done:
A.
Serum analysis of:
Sodium, potassium, and bicarbonate
Plasma cortisol
Plasma corticotrophin, renin, and aldosterone
B.
Corticotrophin stimulation test: 250 mcg of corticotrophin is administered IV followed by measurement of cortisol 30 min later. Adrenal crisis is highly unlikely if:
Basal total cortisol is greater than 20 mcg/dl.
Post corticotrophin cortisol is greater than 20 mcg/dl.
Treatment of Adrenal Insufficiency
The immediate treatment of acute adrenal crisis rests upon correction of fluid and electrolyte imbalance and hydrocortisone replacement. Treatment should be started promptly after sending the lab samples. Initial therapeutic intervention includes the following:
Infusion of sodium chloride 0.9 % and dextrose 5 %
Hydrocortisone 100 mg IV or IM repeated every 8 h until the results of diagnostic screening tests are available.
If diagnostic screening indicates:
Basal or post corticotrophin cortisol greater than 20 mcg/dl: further hydrocortisone therapy is stopped unless the patient is still critically ill.
Cortisol less than 20 mcg/dl: hydrocortisone therapy is continued by IV or IM route (150–300 mg/day for 2–3 days) until full recovery.
Final diagnosis and evaluation of etiology are done after resolution of acute crisis.
Management during Labor and Postpartum Period
Normal vaginal delivery can be expected for women with adrenal insufficiency. Indication for a caesarean section is similar to that in a normal pregnancy. During labor, the patient’s normal dose of hydrocortisone is doubled. Alternatively, a single dose of hydrocortisone, 50 mg IV, may be administered during the second stage of labor. Before caesarean section, stress dose of hydrocortisone, 100 mg, is administered by IV or IM route at the onset of surgery and continued at intervals of 6–8 h following delivery. The dose is tapered over 48 h to regular replacement dose. Breast-feeding is not contraindicated for patients on treatment.
Hyperaldosteronism
Primary hyperaldosteronism is rare in pregnancy with approximately 31 cases reported worldwide [37, 38]. The majority of reported cases may be due to an adrenal adenoma or hyperplasia.
Hyperaldosteronism in pregnancy is associated with hypertension and hypokalemia in a high proportion of cases. Symptoms include headache, fatigue, weakness, dizziness, and muscle cramps [39]. Pregnancy is characterized by moderate to severe hypertension, proteinuria, placental abruption, intra uterine fetal deaths, or preterm births which is mostly iatrogenic.
Diagnosis
The diagnosis of hyperaldosteronism in pregnancy is challenging. The physiological rise of aldosterone in normal pregnancy overlaps the values seen in hyperaldosteronism. However, suppressed renin levels in this setting are confirmatory of hyperaldosteronism. Findings that aid in reaching a diagnosis include the following: elevated aldosterone levels and suppressed renin levels (imaging with MRI or ultrasonography).
Management
Unilateral adrenalectomy in midtrimester is advocated for unilateral macroadenoma. Successful surgery results in normalization of elevated blood pressure as well as serum potassium in majority of cases. Medical therapy is advocated in cases of adrenal hyperplasia or adrenal adenoma identified late in pregnancy. Conventional antihypertensive therapy, otherwise considered safe in pregnancy, like methyldopa and calcium channel blockers, is not very effective. Drugs with specific aldosterone receptor blockade activity, e.g., spironolactone and amiloride, are largely contraindicated in pregnancy.
Pheochromocytoma
Pheochromocytoma is a paraganglioma, a rare catecholamine-producing tumor derived from chromaffin cells that can be fatal if left untreated. They occur mainly in adrenals and less commonly in extra adrenal sites. Twenty-four percent of pheochromocytomas have hereditary basis.
Characteristically, patients present with sustained or paroxysmal episodes of hypertension, headache, palpitations, and pallor. The triad of headache, palpitations, and sweating is often seen. Emergency situations occur owing to high levels of catecholamines secreted by the tumor. Antenatal diagnosis results in improved outcomes but pheochromocytoma can be missed because of unexpectedly normal blood pressure during gestation [40, 42].
Pheochromocytoma can be present as an acute emergency in varied ways:
1.
Multisystem failure: a temperature greater than 40° centigrade, encephalopathy, hypertension or hypotension, pulmonary edema, acute renal failure, and DIC. The clinical features may be mistaken for septicemia.
2.
Cardiovascular emergencies: hypertensive crisis, shock, hypotension, acute heart failure, myocardial infarction, arrhythmias, cardiomyopathy, myocarditis, dissection of aortic aneurysm, and acute peripheral edema.
3.
Pulmonary emergencies: infrequently, pulmonary edema is the presenting feature of pheochromocytoma which may be cardiogenic or noncardiogenic in origin.
4.
Gastrointestinal emergencies: severe abdominal pain and vomiting may indicate hemorrhage of the tumor or spasm of mesenteric arteries causing bowel ischemia.
5.
Nephrogenic emergencies: rarely pheochromocytoma may present as acute renal failure.
6.
Neurological emergencies: cerebral hemorrhage, subarachnoid hemorrhage, and seizures have been reported during attacks of paroxysmal hypertension.
If pheochromocytoma is unsuspected in pregnancy, it can lead to very high rates of morbidity and mortality. Pregnancy-related life-threatening situations can occur owing to tumor stimulation by pressure from enlarging uterus, by fetal movements, by abdominal palpation, or during labor in a patient with unsuspected pheochromocytoma. In one series, diagnosis made in antenatal period reduced maternal and fetal mortality to 1 and 15 %, respectively [43].
Diagnosis
Diagnosis of pheochromocytoma in pregnancy can be difficult because the clinical features resemble preeclampsia. But in contrast to preeclampsia, hypertension in pheochromocytoma can occur throughout pregnancy. Edema and proteinuria are often absent. Furthermore, pheochromocytoma-associated hypertension is paroxysmal and may be accompanied by postural hypotension [41]. New sensitive and specific biochemical tests and imaging aid in reaching the diagnosis.
Fractionated urinary metanephrines and plasma metanephrines estimation are sensitive tests for diagnosis of pheochromocytoma in nonpregnant patients, but their values in pregnancy have yet to be fully evaluated in pregnancy [44].
MRI (without gadolinium) has better sensitivity than an ultrasound scan. Pheochromocytoma is typically bright on T2-weighted MRI with a sensitivity of 93–100 % [45].
Treatment
If diagnosis is made early in pregnancy, adrenalectomy is the preferred definitive treatment of pheochromocytoma following adequate alpha and beta blockade for at least 2 weeks before surgery. The optimal timing of adrenalectomy is late in first trimester or early second trimester. In the third trimester, a combined caesarean section followed by adrenalectomy may be considered.
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