EM Didactic: Endocrine

Monday, October 30, 2017

Thyroid Storm

Thyroid hormone exists in two forms: thyroxine and triiodothyronine. The ratio of thyroxine to triiodothyronine released in the blood is about 20:1 and peripherally, thyroxine is converted to the active triiodothyronine (T3), which is three to four times more potent than thyroxine.

Basic Terminologies

Primary hyperthyroidism is caused by the excess production of thyroid hormones from the thyroid glands.
Secondary hyperthyroidism is caused by the excess production of thyroid-releasing hormones (Hypothalamus) or thyroid-stimulating hormones (Pituitary).

Hyperthyroidism refers to excess circulating hormone resulting only from thyroid gland hyper function. Most commonly cause by Graves' Disease.
Thyrotoxicosis refers to excess circulating thyroid hormone originating from any cause.
Thyroid storm is an extreme manifestation of thyrotoxicosis. It presents as an acute life-threatening hypermetabolic state caused either by excessive release of thyroid hormones or due to altered peripheral response to thyroid hormone following a precipitating event.

Causes of Hyperthyroidism

Graves' Disease
Toxic Goitre
Thyroiditis (Viral, Radiation)
Hashimoto's
Secondary (Pituitary or Hypothalamus related)
Thyrotoxicosis Factitia
Drug Induced (Amiodarone, Interleukin 2)
Metastatic (Struma Ovarii)
Hydatidiform Mole

Precipitants of Thyroid Storm

Trauma
Heat related Illness
Recreational Drug Use
Psychosis
Stress
Infection
Iodinated Contrasts
ACS
DKA/HHS
Thyroxine Overdose

Consider thyroid Strom in any patient presenting with fear, tachycardia and altered mental status. Use Burch-Wartofsky scale to gauge your suspicion and diagnosis.

Management

Following the order of treatment is of utmost importance here. Inhibition of thyroid gland synthesis of new thyroid hormone with a thionamide (Methimazole or PTU) must be initiated before iodine therapy.

1. Supportive care

ABC
Cardiac Monitor and IV accsess.
Fluids, Maintenance of Electrolytes and Glucose. Cooling for hyperthermia.
Add antibiotics as infection is a known precipitant and hard to distinguish in ED
Consider Cholestyramine to decrease the reabsorption of thyroid hormone from the enterohepatic circulation. In thyrotoxicosis, there is increased enterohepatic circulation of thyroid hormone.

2. Inhibition of new hormone synthesis

Thionamides: Methimazole or PropylThioUracil. Thionamides decrease the synthesis of new hormone production.

Methimazole: 40 to 100 milligrams PO as loading dose then 20 milligrams q4h

Propylthiouracil: Load with 600 to 1000 mg PO followed by 200 to 250 milligrams every 4 hours. PTU is hepatotoxic but in addition to decreasing the synthesis of new hormone production, it also blocks the peripheral conversion of thyroxine to triiodothyronine.

Use PTU in first trimester and Methimazole in second and third trimester.

3. Inhibition of thyroid hormone release

Potassium iodide can be given to stop thyroid hormone release. PTU or Methimazole must be started first and Iodine therapy should be given at least 1 hour later. Iodine therapy blocks the release of pressured hormone. Start with 8 to 10 drops initially.

Iodine-containing solutions should not be given to patients with iodine overload or iodine-induced hyperthyroidism or amiodarone-induced thyrotoxicosis. Lithium or potassium perchlorate should be used instead.

4. Peripheral β-adrenergic receptor blockade

Propranolol can be given IV in slow 1- to 2-milligram boluses q5-10min. Orally, propranolol therapy usually begins at 20 to 120 milligrams per dose.

5. Preventing peripheral conversion of thyroxine to triiodothyronine
The peripheral conversion of thyroxine to triiodothyronine is blocked by propylthiouracil, propranolol, and glucocorticoid. Glucocorticoids are essential in treatment since blockade produced by propylthiouracil and propranolol is not significant. . Glucocorticoid also treat underlying relative adrenal insufficiency.

6. Find and treat the precipitation event (Sepsis, DKA, ACS)
7. Definitive Treatment - Radioactive Iodine or Surgery

Other potential considerations:

Direct removal of thyroid hormone with plasma exchange
Use of Potassium Perchlorate in Amiodarone induced thyrotoxicosis: Potassium perchlorate interferes with the production of new hormones
Lithium: Used in cases of hypersensitivity to iodine. Lithium inhibits thyroid hormone release from thyroid gland. Typical dosing in thyroid storm is 300 milligrams every 8 hours. Monitor levels to avoid toxicity.
Peripheral beta blockade: Reserpine or Guanethidine can be used, if there is a contraindication for BB use. These agents do not block beta receptors and interfere with catecholamine function (by depleting stores and blocking release)

Take Home:

Consider Thyroid Strom in any patient presenting with fever, tachycardia and Altered Mental Status.
PTU or Methimazole must be started first and Iodine therapy should be given at least 1 hour later.
Manage with beta blockers, PTU/Methimazole, Steroids and Potassium iodide
Identify and treat the precipitation cause

Further Reading

Posted by:

Lakshay Chanana

Speciality Doctor

Northwick Park Hospital

Department of Emergency Medicine

England

@EMDidactic

Monday, October 9, 2017

Hyperosmolar Hyperglycaemic State - HHS

HHS is a syndrome charcaterised by hyperglycemia and hyperosmolarity commonly precipitated by an illness (infection, infarction, any other illness or stress ). Classically, HHS is seen in frail elderly patients with poor thirst perception and uncontrolled diabetes mellitus.

Pathophysiology

Relative Insulin Deficiency-->Hyperglycaemia-->Osmotic Diuresis-->Dehydration and electrolyte loss. There is lack of severe ketoacidosis in HHS possibly due to higher levels of endogenous insulin and lower levels of counter-regulatory hormones.

Changes in serum osmolality and Na explain mental status changes and coma. The normal serum osmolality ranges between 275 to 295 mOsm/kg. Values >320 mOsm are commonly associated with altered mental status.

Diagnostic Criteria

Severe hyperglycemia with serum glucose usually >600 milligrams/dL (>33.3 mmol/L)
Elevated calculated plasma osmolality of >315 mOsm/kg
Serum bicarbonate >15 mEq/L (>15 mmol/L)
Arterial pH >7.3, with negative to mildly positive serum ketones

Occasionally, it can be challenging to differentiate HHS from DKA. HHS may present with metabolic acidosis or ketonemia due to lactic acidosis, starvation ketosis, and renal failure in various combinations. Type 1 diabetics may present with HHS and Type 2 may are known to have DKA as well. It is important to recognize the mixed acid-base patterns in patients in these hyperglycaemic syndromes.

Management

Fluid Resuscitation to improvement of tissue perfusion (Average fluid deficit is 8-12 litres)
Insulin Drip (after initial fluid rests and ensuring normal K level)
Identify and treat the precipitating cause
Correct electrolyte abnormalities (HypoK, HypoMg)
Gradual correction of hyperglycaemia

Initial investigations include a complete metabolic profile, calculated and measured serum osmolality, coags, blood gas, CRP, Renal Function, serum ketones, FBC, blood and urine cultures should all be considered, Chest radiographs and electrocardiograms. Consider CT when suspecting a CNS infection or poor response to initial therapy.

Management need to individualised with concurrent medical illnesses (CCF, CKD). Once serum glucose <300 milligrams/ dL (<16.6 mmol/L), switch to 5% dextrose in half normal saline, and reduce the insulin infusion to 0.02 to 0.05 unit/kg/h and glucose is maintained between 200 and 300 milligrams/dL (11.1–16.6 mmol/L).