Life-Threatening Inpatient Endocrine Emergencies

While Nashville’s honky-tonks and hot chicken stressed our endocrine systems, one talk at SHM Converge gave us the tools to master the metabolic chaos of true endocrine emergencies we may face in the hospital. The session included a series of cases where hormonal imbalances may lead to life-threatening emergencies, including adrenal, thyroid, and pituitary abnormalities. While these emergencies are rare, the stakes are high given the elevated mortality when present. They are diagnostically challenging, masquerading as other etiologies. In addition to addressing these acute emergencies, Dr. Ackermann addressed perioperative management tips and transitions of care.

One overarching message predominated, which is to treat the patient and not the number. A thyroid-stimulating hormone level does not define myxedema coma, and a cortisol level does not reliably define adrenal insufficiency in the critically ill. Pattern recognition and clinical acumen remain the indispensable tools.

Acute Post-Operative Hypocalcemia

Dr. Ackermann began with a case of a patient who developed carpopedal spasm, perioral paresthesia, and a facial twitch after total thyroidectomy. While we associate hypocalcemia with parathyroid surgery, hypocalcemia is even more common after total thyroidectomy, occurring in 20% to 50% of patients within 24 to 72 hours. Severe hypocalcemia (ionized calcium below 4 mg/dL, total calcium below 7 mg/dL) occurs in 5% to 6% of patients post total thyroidectomy, with the highest risk occurring in patients with Graves’ disease.

Acute management of hypocalcemia includes treatment with 100 to 300 mg of IV calcium gluconate over five to 10 minutes, then a calcium drip while following levels every four to six hours. The risk of hypocalcemia can be determined postoperatively if the postoperative parathyroid hormone level is greater than 15 pg/mL and the calcium is greater than or equal to 8 mg/dL. Other patients should remain inpatients to be monitored for ionized calcium levels and for early intervention for drops in calcium levels.

Clinical Pearls

• Refractory hypocalcemia may reflect hypomagnesemia or hypokalemia, and this should always be repleted.
• Start oral calcium 3,000 mg/day and calcitriol 0.25 mcg twice daily as soon as possible, along with the IV repletion. This can be started as prophylaxis against an acute drop.
• Those with end-stage renal disease and tertiary hyperparathyroidism with a parathyroid hormone level greater than 1,000 pg/mL and alkaline phosphatase greater than 300 IU/L preoperatively are at the highest risk for hungry bone syndrome, which causes rapid and catastrophic hypocalcemia within 18 to 24 hours postoperatively.
• Thyroid Emergencies: Not Just the TSH Level

While checking an inpatient’s thyroid-stimulating hormone (TSH) level can be a “thing we do for no reason” when thyroid illness is driving severe illness, it is necessary, but the level can be misleading.¹ The level does not correlate with the severity of illness. Myxedema coma has a mortality rate of 60%, so diagnosis is critical. Dr. Ackermann discussed the diagnostic scoring system for myxedema coma as a way to score patients on thermoregulatory dysfunction, central nervous system effects, gastrointestinal findings, a precipitating event, cardiovascular dysfunction, and metabolic disturbances, with scores greater than 60 being diagnostic, and scores 25 to 59 being suggestive.² Treatment should be started urgently with 100 mg of IV hydrocortisone (HC) every eight hours after adrenal hormone levels are drawn. IV levothyroxine treatment at an initial dose of 4 mcg/kg of IV levothyroxine, followed by daily dosing of 1.6 mcg/kg IV. Additional support for a patient’s airway and intensive care unit admission is necessary. Passive rewarming should be done, as active rewarming may have a risk of vasodilation.

Clinical Pearls

• Dose reduce levothyroxine in elderly patients and patients with cardiac disease by 25%, as rapid normalization of metabolic rate will increase myocardial oxygen demand.
• Passive rewarming is required prior to fluid resuscitation.
• Steroids can be tapered based on clinical response.

When the thyroid becomes hyperactive, it goes along a spectrum from a normal state to subclinical hyperthyroidism, thyrotoxicosis, and ultimately thyroid storm, which carries a mortality rate as high as 40%. The Burch-Warofsky Score for thyrotoxicosis can help grade severity based on temperature, central nervous system changes, gastrointestinal changes, heart rate, heart failure or atrial fibrillation, and presence of a precipitant.3 Hyperthyroid crises are triggered by a rapid rise in thyroid hormone and acute or subacute non-thyroidal illness, with the most common triggers being withdrawal of anti-thyroid therapy and infection. Iodinated contrast dye from CT scans in undiagnosed Graves’ patients is key to watch out for.

Treatment has four underlying steps: 1) beta-blockade, 2) anti-thyroid drugs, 3) iodine, and 4) steroids. Beta-blockade should use propranolol or IV esmolol to block peripheral adrenergic effects. Propylthiouracil (PTU) should be used in thyroid storm and later converted to methimazole for long-term use.  A stress dose of HC 100 mg IV every eight hours is indicated to block T4 to T3 conversion, as well as to address possible concurrent adrenal insufficiency.

Clinical Pearls

• Wait at least one hour after giving PTU prior to starting iodine therapy.
• In the elderly, thyrotoxicosis can present atypically, as more than 50% of older patients have fewer than two symptoms.

Adrenal Crisis

Adrenal insufficiency typically presents with non-specific symptoms, including fatigue, depression, nausea, vomiting, and abdominal pain. An evolving crisis may add some metabolic abnormalities, including elevated blood urea nitrogen, hyponatremia, metabolic acidosis, and hyperkalemia. An adrenal crisis then may add fever, anorexia, shock, and cardiovascular collapse, leading to overall 0.5% mortality, but elevated to 15% in those with Addison’s. Three patient profiles to be wary of include oncology patients, patients on chronic steroids, and critically ill patients. In oncology, adrenal insufficiency may be caused by metastatic disease, new treatments like checkpoint inhibitors, or old treatments like radiation. Adrenal insufficiency may develop if on more than 5 mg/day of chronic glucocorticoids for more than three weeks. Critical illness may lead to adrenal insufficiency in a variety of ways.

For acute adrenal crisis, hormonal testing with adrenocorticotropic hormone (ACTH) and cortisol should be performed. Initial treatment consists of a bolus of HC 100 mg IV with an additional 200 mg IV over the following 24 hours in divided doses, with standard dosing as 100mg IV every eight hours. This can be tapered on day three to 60 mg IV every 24 hours until stable and out of the intensive care unit, which can then be tapered to a stable maintenance dose.

For critical illness, ACTH and cortisol testing are not needed, and HC 200 mg IV every 24 hours should be started in refractory septic shock. Corticosteroids may help resolve sepsis and shock sooner, but they do not affect mortality.

Clinical Pearls

• Fevers can be exaggerated by low cortisol levels, but one must assume infection.
• Elevated TSH may occur in adrenal insufficiency as a lack of cortisol suppresses TSH, but thyroid replacement may precipitate an acute crisis.
• A morning cortisol greater than or equal to 10 mcg/dL makes the likelihood of clinically relevant adrenal insufficiency quite low.
• Fludrocortisone 0.1 mg daily is added in primary adrenal insufficiency once the HC dose is tapered below 40 mg/day.
• Prolonged critical illness may cause critical-illness-related corticosteroid insufficiency, requiring ongoing HC supplementation.

Pituitary Apoplexy

Dr. Ackerman’s last clinical case involved a 65-year-old man who developed a sudden severe headache, altered mental status, nausea, vomiting, and acute diplopia and ophthalmoplegia along with sudden panhypopituitarism consistent with acute pituitary apoplexy. Typically, this occurs due to acute hemorrhage or infarction of a pituitary adenoma. Bleeding causes increased intracranial pressure, cranial nerve involvement, and parenchymal pituitary injury. A CT is the first imaging step, but an MRI will be more sensitive to the amount of tissue involvement. This requires immediate neurosurgical intervention along with neuro-ophthalmology and endocrinology specialists. Patients require immediate stress-dose steroids and evaluation for other hormonal deficiencies; 70% will need surgical decompression.

Endocrine Perioperative Considerations

Endocrine emergencies should delay surgery unless the surgery is emergent and a life-or-death scenario. For minor and moderate abnormalities, consider the following:

Hypothyroid patients:

• Subclinical hypothyroidism: may proceed for elective and urgent cases
• Overt hypothyroidism: delay elective cases until oral levothyroxine achieves euthyroid status; may proceed in urgent cases with oral replacement

Hyperthyroid patients:

• Subclinical hyperthyroidism: proceed and consider beta-blockers in older patients or those with arrhythmias.
• Overt hyperthyroidism: delay elective cases for three to eight weeks until thyroid function tests normalize. For urgent procedures, start iodine, thioamides, and a long-acting beta-blocker.
• Adrenal insufficiency: Perioperative adrenal crisis is rarer than traditionally taught (incidence less than 1%). Stratify patients by diagnosis, chronic steroid dose, and surgical stress as follows:
  • Minor stress (e.g., inguinal hernia): 25 mg IV HC or usual dose
  • Moderate stress (e.g., joint replacement): Single dose 50 mg IV HC followed by 25 mg IV every eight hours, tapered over one to two days
  • Major stress (e.g., coronary artery bypass graft): 100 mg IV HC followed by 50 mg IV every eight hours, tapered over two to three days

Discharge Planning: Preventing the Next Emergency

Endocrine emergencies are disproportionately driven by medication non-adherence, delayed recognition of warning signs, and system failures in care coordination. Ensure an adequate supply of medication at discharge, verify insurance coverage, and confirm that the patient or caregiver understands the regimen. Patient education should review warning signs. For adrenal insufficiency in particular, patients must know sick-day rules, and every adrenal-insufficient patient should carry a medical alert card and an emergency injection kit. Post-thyroidectomy patients must recognize tingling around the mouth and fingertips and know to take 1,000 mg of calcium immediately and call their providers.

A direct provider handoff from the hospitalist to the primary care physician and endocrinology should occur; their follow-up appointment should be within one to two weeks, with labs ordered and arranged before discharge. Social work support should be initiated for patients with transportation barriers, food insecurity, limited health literacy, or language barriers, all of which increase the risk of medication non-adherence and delayed crisis recognition. Telehealth options can bridge geographic and access gaps for vulnerable populations. 

Dr. Molitch-Hou

Dr. Molitch-Hou is an assistant professor, the director of the hospital medicine sub-internship, core faculty for the internal medicine residency program, and co-director of the care transition clinic at the University of Chicago Medical Center in Chicago.

References

1. Wootton T, Bates R. Things We Do for No Reason™: routine thyroid-stimulating hormone testing in the hospital. J Hosp Med. 2020;15(9):560-562. doi:10.12788/jhm.3347.
2. Popoveniuc G, et al. A diagnostic scoring system for myxedema coma. Endocr Pract. 2014;20(8):808-817. doi:10.4158/EP13460.OR.
3. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22(2):263-277.