Inpatient Endocrine Emergencies

Michael Shannon, MDProvidence Endocrinology, Olympia WA

Endocrine Inpatient Issues

Hyperthyroidism and thyroid stormMyxedema comaNon-thyroidal illnessAcute adrenal insufficiencyHypercalcemiaPituitary apoplexy

Diabetes in Hospital Settings

Estimated that 18% of admissions have diabetes, and that diabetics account for 24% of the length of stay for all inpatient daysThere is improved recognition that elevated sugars are not benign from stress and lead to (increasingly uncompensated) complications such as urinary tract infections, poor wound healing, and dehydration

Thyroid Storm

Thyroid storm is an extreme form of thyrotoxicosis (usually with a precipitating cause – MI, infection)Manifested by marked delirium, severe tachycardia, dehydration, and very high fever;Diagnosis is history and physical; labs show very low TSH, high free T4 and T3 (TSH is most reliable)

Franklyn JA, NEJM 1994.

Hyperthyroid vs Thyroid Storm

Note that findings are not different than that of hyperthyroidism, but the difference is in the setting; key is fever (typically > 40 C / 104 F)You can be admitted with hyperthyroidism that is severe yet is not thyroid storm (hyperthyroid tachyarrhythmias are serious but not “storm”)Thyroid hormone levels are not much different in storming than in other cases so likely other predisposing factors (stress, metabolic factors)

Etiology of Thyroid Storm

Most thyroid storm is from Graves’ diseaseVery small number of cases from toxic nodule or multi-nodular goiterUsually unstable for scan; TSI Ab helpful

Treatment of Thyroid Storm

This is an ICU level admissionMajor part is supportive care with hydration, cooling blankets, and antipyretics (acetaminophen)Avoid aspirin (case reports that it releases thyroid hormone from its binding globulin, worsens case)Intensive therapy with anti-thyroid drugs, beta-blockers, steroids, iodine solutions

Treatment of Thyroid Storm

1. Beta-blockade: propranolol 20-60 mg q6h (can also give intravenously)

2. Anti-thyroid drugs: Usually methimazole used for outpatients, but here PTU at high doses will both lower synthesis and T4->T3 peripheral conversion; 150 mg q6hrs

3. Iodine agents4. Steroids

Treatment of Thyroid Storm

1. Beta-blockade2. Anti-thyroid drugs3. Iodine agents: utilize the Wolff-Chaikoff effect

where high dose iodine suppresses thyroid hormone production (hard to find: SSKI drops or Lugol’s solution – popular with naturopaths)

4. Steroids: dexamethasone 2 mg q6h to drop circulating T3 levels and suppress T4 -> T3 conversion

Myxedema Coma

Severe hypothyroidism with metabolic shutdown (cardiac, hepatic, other organs)Often comatose or deliriousDry coarse skin, hoarse gravelly voice, thin dry hairHypothermiaPericardial and pleural effusions

Myxedema: Pathophysiology

Myxedema: Diagnosis and Etiology

Diagnosis is made with clinical scenario and TSH through the roof – usually >80Can also have a very low free T4 with a slightly elevated TSH if pituitary failure (rare)Three major etiologies:

Undiagnosed hypothyroidism (autoimmune thyroiditis, radiation hypothyroidism, etc)More commonly discontinuation of therapy or running out of medication (for months)Iatrogenic: stopping patients for I-131 cancer Rx

Myxedema Treatment

Initial therapy is supportiveRewarming protocolSupport BP and respiration (usually low-output CHF)

Levothyroxine: 250 mcg intravenous x 3 days load, then 100 mcg (or old dose) orally per dayMay use liothyronine (Cytomel) 12.5 mcg TID x3 days

Nonthyroidal illness (NTI)

Also known as euthyroid sick syndrome; this occurs when there is inhibition of the thyroid deiodinase, reducing the levels of T3This is “all levels down” thyroid pattern; decreased TSH, decreased T4, decreased T3Challenge is differentiating thyroid levels as a result of illness versus the cause of it (classic conundrum: manic episode with TSH 0.2)

Nonthyroidal illness: Lab Patterns

Diagnostic Challenges: NTILow FT4: NTI versus hypothyroidism; use the TSH

Clinical signs, eg bradycardia, hypoventilation, hypothermia>20 mU/ml: primary hypothyroidism5-20: primary hypothyroidism vs NTI; repeat in 1-2 weeks or treat empirically and reassess as outpatient<5: NTI vs secondary hypothyroidism; History or evidence of pituitary disease?

Low TSH: NTI vs hyperthyroidism; use the free T4Clinical signs, including atrial fibrillation

Low-normal : probably NTI, especially if TSH >0.1 μU/mlHigh: hyperthyroidism

For modest deviations – time is your friend!

Adrenal Insufficiency and Crisis

Adrenal failure: Presentation

Weakness & fatigueAnorexia & weight lossNausea & vomitingDizziness and orthostatic symptomsLethargy, stupor

HyponatremiaHypotensionShock & death

Hyperkalemia*Hyperpigmentation*

*Only in primary adrenal failure

Dusky Hyperpigmentation

Adrenal failure: causes

Primary (cortisol & aldosterone deficient)AUTOIMMUNEtuberculosis, fungal infectionsHemorrhage, sepsis, etc

Secondary (ACTH & cortisol deficient)GLUCOCORTICOID THERAPYhypothalamic or pituitary lesions

Adrenal failure: evaluation

Dexamethasone 10 mg IV if hypotensiveCortrosyn stimulation test:

Cortrosyn 250 mcg IVPlasma cortisol @ 60 minNormal: >20 mcg/dL or stimulate > 9 mcg/dLNot sensitive for new onset secondary adrenal Not sensitive for new onset secondary adrenal failurefailure

Eg, after pituitary surgery, pituitary apoplexyTreat empirically with prednisone for 4 weeksHold prednisone AM of test

Adrenal failure:emergency therapy

Indications:HypotensionStupor/deliriumSevere abdominal pain and intractable nauseaSevere hyperkalemia or hyponatremia

Hydrocortisone 100 mg IV Q 8 hrD5/normal saline to hydrateThen double the outpatient dose for three daysGet them a Medic-Alert bracelet!

Failures of Adrenal Treatment

Running out of meds, no sick day plan, no bracelet.

Steroid coverage

Indications:Known adrenal failureChronic steroid treatmentRecent (1 year) chronic steroid treatment (prednisone 7.5 mg/dayfor two months in the last twelve)

For severe illness, major surgery:Hydrocortisone 50 mg IV Q 8 hr

For moderate illness, minor surgeryHydrocortisone 25 mg IV Q 8 hr

Post-op or during hospitalization, double dose for three days then taper to chronic replacement over 2-3 days

Hypercalcemia: Presentation

System Common--------------------------------Rare

CNS Fatigue, weakness, depression, confusion

GI Constipation, anorexia, N+V, pancreas

Renal Poly’s, dehydration, stones, calcinosis

Cardiac --------palp, rhythm, brady, short QT

Hypercalcemia: Differential

Common Uncommon Rare

Primary HPTHMalignancy

Milk-AlkaliSarcoidosisDrugs (Li, VitD)Renal failureTPNThyrotoxicosis

Pheo, VIPomaFHHTuberculosisHistoplasmosisHypoAlkPhosImmobilization

Hypercalcemia: Malignancy

1. PTHrP (i.e. squamous cell carcinoma)2. Cytokine release (i.e. multiple myeloma)3. Lytic bone disease (i.e. breast cancer)4. Excess Vitamin D production (i.e.

lymphoma)

Hypercalcemia: When to Treat

Severe symptoms of hypercalcemiaPlasma [Ca] >13 mg/dlWhere possible send laboratories beforehand

Calcium with intact PTHIf PTH is anything but low or low-normal, it is primary hyperparathyroidism

If malignancy, consider no treatment – there are worse deaths than hypercalcemic delirium (average lifespan is 6 weeks with this)

Severe hypercalcemia: therapyRestore ECF volume

Normal saline rapidlyPositive fluid balance >2 liters in first 24 hr

Saline diuresisNormal saline 100-200 ml/hrReplace potassiumOnly after full volume repletion

Zoledronic acid 4 mg IV over 15 minIf plasma [Ca] >14 mg/dl or >12 mg/dl after rehydrationMonitor plasma calcium QD

Pituitary Apoplexy

Pituitary Apoplexy

Hemorrhage into a pituitary adenoma; sudden increase in pressure typically presents with severe headache, nausea, vomitingSevere headache usually leads to CT/MRI showing pituitary mass with acute bleedingThis is a neurosurgical emergency if severe enough, if the hemorrhage endangers optic chiasm; need surgery unless prolactinomaGoal is to check/replace steroids and thyroid

A hospital is no place to be sick.

Samuel Goldwyn (1882-1974)

Question and Answer

Thank you for allowing me to review endocrine consult issues and support your patients’ endocrine needs.