Sandbox: HS

The mainstay of treatment for secondary adrenal insufficiency is identifying and treating the underlying cause and replacement of deficient hormones which is mainly cortisol in this case.

• Adrenal crisis is mainly seen with primary adrenal insufficiency or Addison's disease. However, it can also manifest in secondary or tertiary adrenal insufficiency in the events of acute illnesses.

Acute secondary adrenal insufficiency or adrenal crisis management

The mainstay of treatment includes glucocorticosteroids and supportive therapy.

• Maintain airway, breathing, and circulation.
• Normal saline 0.9% or 5% dextrose in normal saline should be administered to correct hypotension and dehydration.
• Supplementation of adequate glucocorticoids.
• Careful monitoring of blood pressure, fluid status, and serum sodium and potassium levels should be maintained.
• Hypotension seen in secondary adrenal insufficiency is due to loss of vasomotor tone and not mainly due volume loss.

Longterm management

The long-term treatment goal is to maintain normal blood pressure, blood glucose, and fluid volume, and a sense of well-being in the patient.

• Adequate daily supplementation of glucocorticoid to mimic normal physiology.
• Supplementation of ACTH and other pituitary hormones in case of hypopituitarism. The replacement of thyroid hormone without replacing glucocorticoid can cause adrenal insufficiency.
• Advise patients on medication for minor illness (febrile illness or emesis) to double or triple their usual dose of glucocorticoid. In case of severe illness, they should inject themselves with a large dose of glucocorticoid and seek immediate medical attention.

Patients with secondary adrenal insufficiency should receive evaluation and adequate replacement for other pituitary hormone deficiencies. Replacement of thyroid hormone without replacement of glucocorticoids can precipitate acute adrenal insufficiency. ●Patients with hypopituitarism who have partial or total ACTH deficiency and are receiving suboptimal cortisol or cortisone replacement may be at risk of developing symptoms of cortisol deficiency when growth hormone therapy is initiated. This is due to the inhibitory effect of growth hormone on 11-beta-hydroxysteroid dehydrogenase type 1, the enzyme that converts cortisone to cortisol [35]. Illness or surgery — Cortisol secretion normally increases with the stress of illness and surgery. This fact has prompted the usual clinical practice of giving higher doses of glucocorticoid to patients with adrenal insufficiency in these situations. Unfortunately, there is little information about how much additional glucocorticoid is needed.

Illness — During minor illnesses, such as upper respiratory infections, the patient can increase the dose of glucocorticoid to two to three times the usual daily dose for three days without consulting a clinician (known as the 3 x 3 rule). The increased dose will decrease fever and malaise and will not compromise the immune response. If the illness becomes worse during the three days or if the patient cannot resume the usual maintenance dose on the fourth day, he or she should consult a clinician to determine if other treatment (eg, antibiotics) is indicated.

As described below, patients with nausea and vomiting who are unable to retain oral medications should have a low threshold for injecting glucocorticoid. Further medical attention should then be sought. (See 'Emergency precautions' below.)

Surgery — The appropriate dose and timing of glucocorticoids for patients undergoing surgery is controversial. Early reports of death after surgery led to a recommendation to give glucocorticoids in doses equivalent to 1000 mg of hydrocortisone daily [46]. This is clearly in excess of the increased production of up to 200 mg daily. Prolonged postoperative pharmacologic glucocorticoid therapy can mask symptoms and signs of infection and cause undesirable side effects. For example, traditional doses of 300 to 400 mg hydrocortisone for a few days can cause significant hypokalemia and edema. (See "The management of the surgical patient taking glucocorticoids".)

Current recommendations for glucocorticoid supplementation at surgery take into account the severity of the operation and suggest lower daily doses [46,47]. For minor procedures such as herniorrhaphy, a dose equivalent to hydrocortisone 25 mg is suggested for the day of operation only, with a return to the usual replacement dose on the second day. For moderate surgical stress (eg, cholecystectomy, joint replacement), divided intravenous (IV) doses equivalent to hydrocortisone 50 to 75 mg are suggested on the day of surgery and the first postoperative day, with a return to the usual dose on the second postoperative day (using oral or IV preparation as appropriate). The authors suggest a total daily dose equivalent to 100 to 150 mg hydrocortisone for major surgical procedures (eg, cardiac bypass) given in divided doses for two to three days, then returning to the usual dose. Alternatively, the dose used on the day of surgery can be halved on postoperative day one. (See "The management of the surgical patient taking glucocorticoids".)

Emergency precautions — The major risk to the patient with adrenal insufficiency is the lack of a normal serum cortisol response to stress and, in patients with primary adrenal insufficiency, of a normal renin-angiotensin-aldosterone response to hypovolemia. Consequently, the patient must anticipate these situations and be prepared to modify therapy to meet these needs.

Every patient should wear a medical alert (Medic Alert) bracelet or necklace and carry the Emergency Medical Information Card that is supplied with it. Both should indicate the diagnosis, the daily medications and doses, and the clinician to call in the event of an emergency.

Each patient should have injectable glucocorticoid, such as 100 mg vials of hydrocortisone (Solu-Cortef) or 4 mg vials of dexamethasone, along with vials of sterile 0.9 percent normal saline and syringes. The patient and one or more responsible family or household members should be instructed on how to reconstitute and inject the medication subcutaneously or intramuscularly anywhere on the patient's body if any of the following occur:

●An injury with substantial blood loss (more than a cup) or fracture ●Nausea and vomiting and inability to retain oral medications ●Symptoms of acute adrenal insufficiency ●The patient is found unresponsive The entire dose of medication should be injected (100 mg of hydrocortisone or 4 mg dexamethasone). Patient and family instruction should include the need to get medical help immediately after the injection. The patient should be instructed to have a low threshold for injecting the glucocorticoid: if it might be necessary, it should be injected and medical attention should be sought. It is unlikely, however, that a patient will need the injectable glucocorticoid more than two or three times a year, and most patients go for years without using it.

Critical illness — Adrenal cortisol secretion increases during critical illness, but the increase may not be detected if only total serum cortisol concentrations are measured. Some critically ill patients may have "functional adrenal insufficiency," but there is currently no consensus on diagnostic criteria or indications for treatment. This topic is discussed in detail separately. (See "Glucocorticoid therapy in septic shock", section on 'Relative adrenal insufficiency' and "Evaluation of the response to ACTH in adrenal insufficiency".)

The exact incidence of HHS is not known, but it is estimated to account for <1% of hospital admissions in patients with diabetes (1)

Centers for Disease Control and Prevention. Diabetes Public Health Resource: Diabetes Data & Trends. Available at: http://www.cdc.gov/diabetes/statistics/mortalitydka/fratedkadiabtotals.htm

Most cases of HHS are seen in elderly patients with type 2 diabetes; however, it has also been reported in children and young adults (2). The overall mortality rate is estimated to be as high as 20%, which is about 10 times higher than the mortality in patients with diabetic ketoacidosis (DKA) (3–5).

The reported mortality is between 10 and 20%, which is about 10 times higher than the mortality rate in patients with diabetic ketoacidosis (DKA). Despite the severity of this condition, no prospective, randomized studies have determined best treatment strategies in patients with HHS, and its management has largely been extrapolated from studies of patients with DKA. There are many unresolved questions that need to be addressed in prospective clinical trials regarding the pathogenesis and treatment of pediatric and adult patients with HHS.

Population-based data are not available for HHS. The rate of hospital admissions for HHS is lower than the rate for DKA, and accounts for less than 1 percent of all primary diabetic admissions [1,3-5].

The mortality rate for hyperglycemic crisis declined between 1980 and 2009

HHS

Fluids

Insulin

Potassium

If serum glucose does not fall at least 10% in first hour