This document discusses various neuroendocrine emergencies including pituitary apoplexy, myxedema coma, thyroid storm, adrenal crisis, hypercalcemia, hypocalcemia, and hyperglycemic emergencies. Pituitary apoplexy is caused by hemorrhage or infarction of the pituitary gland and presents with sudden severe headache, visual changes, and pituitary hormone deficiencies. Myxedema coma and thyroid storm are life-threatening complications of hypothyroidism and hyperthyroidism respectively that require prompt diagnosis and treatment with thyroid hormones, glucocorticoids, and supportive care. Adrenal crisis occurs in patients with primary or secondary adrenal insufficiency due to inadequate cortisol response to stress

1. Neuroendocrine
Emergencies
DR BHAVIN J PATEL
SR NEUROLOGY
GMC KOTA

2. Introduction
Endocrine emergencies are a collection of rare and extreme manifestations
of common endocrine disorders
Endocrine emergency may be the first presentation of the underlying
endocrine disorder.
The rate of change in hormonal level is important.
 Many of these endocrine emergencies can be successfully managed if
accurately and promptly diagnosed.

3. Neuroendocrinopathy
Pituitary disorders:- pituitary adenoma----pituitary apoplexy
Thyroid disorders:- hypothyroidism----myxedema coma
hyperthyroidism----thyroid storm
Adrenal disorder:- Cushing syndrome
Addison disease----addisonian crisis
pheochromocytoma---Crisis
Adrenoleukodystrophy
Mineral metabolism and parathyroid disorder:- hypoparathyroidism---hypocalcemia
hyperparathyroidism---hypercalcemia

4. Neuroendocrinopathy
Gonadal disorder:- estrogen deficiency in menopause
Testosterone deficiency in elderly male
Paraneoplastic disorder
Obesity:- migraine
polyneuropathy
Diabetes mellitus:-neuropathy
ketoacidosis or HONK
hypoglycemia
Neuroendocrine tumors(NET):- Carcinoid crisis

5. Pituitary apoplexy
Clinical syndrome characterized by sudden hemorrhage or infarction of the
pituitary gland
Most commonly:- pituitary adenoma
Can occur in normal gland:- Sheehan syndrome
Prevalence of 6.2 cases per 100,000 individuals
Incidence of 0.17 episodes per 100,000 per year

6. Pituitary apoplexy
Precipitating factors:-
Angiographic procedures and surgical procedures
 Head trauma,
Pregnancy
Anticoagulant therapy
Stimulation of the pituitary gland through dynamic testing
Certain hormonal treatments
Dopamine agonists

7. Clinical features
Headache:- The most prominent and common symptom
Classically described as a thunderclap headache
Usually retro orbital but can be bi frontal or diffuse
Nausea and vomiting
Ocular symptoms:- Acute onset blindness or change in vision field
Ptosis and Diplopia

8. Clinical features
Hemodynamic instability
Focal neurological deficit
Coma
Examination:-
Dilated pupil with papilledema
3,4 and 6 CN palsy
Neck stiffness

9. Investigation
Hyponatremia
CSF:- pleocytosis and xanthochromia
CT brain:-
CT is diagnostic in only 21% to 28%
 Intrasellar mass can be visualized in up to 80% of pituitary
apoplexy cases
MRI Brain:-
Superior imaging modality
Confirms the diagnosis in over 90% of patients.

10. Treatment
Surgical:-
Altered sensorium with focal neurological deficits
Conservative:-
Empiric corticosteroids
Other supportive treatment
Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy.
Clin Endocrinol (Oxf) 2011;74(1):9Y20.

11. Case 1
A 65-year-old man with hypertension and prostate cancer presented to the
hospital reporting headache and blurry vision. Three days earlier, he had
received his first dose of depot leuprolide for androgen deprivation therapy.
Neurologic examination was notable for a right third cranial nerve palsy.
 MRI of the brain revealed a large intrasellar mass with hemorrhage.
Hydrocortisone was empirically administered, and the patient underwent
transsphenoidal surgery for diagnosis and resection of the intrasellar mass.

12. Addisonian Crisis
Can be secondary to:- primary adrenal insufficiency
Secondary adrenal insufficiency
Iatrogenic (steroid withdrawal– MC)
Infection and severe physiological stress
No administration form, dosing, treatment duration, or underlying disease for
which adrenal insufficiency can be excluded after steroid withdrawal.
8.3 adrenal crisis per 100 patient years
Broersen LH et al. Adrenal insufficiency in corticosteroid use: systemic review and meta-analysis. J Clin Endocrinol
Metab 2015; 100(5):2171Y2180. doi:10.1210/jc.2015-1218.

13. Pathophysiology
Acutely stressful event, a patient with adrenal insufficiency fails to mount a
normal physiologic response of increased endogenous cortisol production
Gastrointestinal illness and fever from an acute infection -- most common
precipitating event
Other events:-
Surgical stress, emotional stress, inadequate exogenous corticosteroid treatment,
insect bites

14. Clinical features
Neurological :-
Altered mental status----delirium, coma
Seizure
Muscle cramp and myopathy
Other systemic manifestations:-
Nausea and vomiting, abdominal pain
Hypotension

15. Investigations
Abnormal findings:-
Hyponatremia
Hyperkalemia (in primary adrenal insufficiency)
Raised BUN and creatinine--- prerenal failure
Hypoglycemia
Hypercalcemia

16. Management
Treatment should be started immediately in patients with known adrenal insufficiency
Patients without a known diagnosis of adrenal insufficiency, treatment should not be
delayed while waiting for a diagnosis.
Diagnostic work up:-
Serum cortisol
Serum ACTH and aldosterone
Serum Renin
Investigation for precipitating event:-CBC, Urine microscopy, Fever profile, Widal

17. Management
Fluid resuscitation and steroid replacement are the main therapies of an adrenal
crisis
Vasopressor may be required in case of persistent hypotension
Correction of hyponatremia
Glucocorticoid therapy:-
 100 mg hydrocortisone IV bolus F/B 200 mg over 24 hr by infusion or IV injections
 Once patient is stable Dose can be tapered to maintenance dose in 1-3 days
 Mineralocorticoid replacement can be started once hydrocortisone dose reduced to <50 mg/d.

18. Case 2
20 yr male----intermittent nausea and headache x 4 days
----- acute onset abnormal behavior with vomiting f/b rapidly worsening level of
consciousness x 1day
-----on admission GCS 13/15 which rapidly worsened and pt was intibated
-----treated with mannitol and dexamethasone----improved and extubated in 17 hrs
Investigations:-
 Culture, toxin screen, CSF:- normal
 CT brain s/o moderate effacement of basal cisterns and a fourth ventricle reduced in size.
 S.cortisol and aldosterone low level, ACTH high
 ACTH stimulation test :- positive
 Anti 21 hydroxylase antibody positive.

19. Myxedema Coma
An infection or another inciting factor in a
hypothyroid patient can lead to an acute
decompensation
Estimated incidence rate of 0.22 per million per
year
Mortality rate:- 20 to 50%
90% of cases occur during the winter months
More common in older women, with 80%
occurring in women older than 60 years
Rodrı ´guez I, et al. Factors associated with mortality of patients with myxedema coma: prospective study J Endocrinol
2004;180(2)

20. Clinical features
Neurological manifestations:-
Depressed mental status---coma
Cerebellar sign
Seizure---status epileptics
Other systemic manifestation:-
CVS:- hypotension, Brady arrhythmia
RS:- breathlessness
GIT:- hematemesis secondary to coagulopathy, abdominal distension

21. Clinical features
Physical examination:-
Hypothermia
Periorbital puffiness
Macroglossia
Signs of pleural effusion or ascites
Non pitting edema
Ecchymosis, purpura
Areflexia

22. Investigations
Normocytic normochromic anemia
Hyponatremia
Metabolic Acidosis
Raised CPK and LDH
CSF:- High opening pressure
Elevated protein
Deranged coagulation profile
EEG:- global cerebral dysfunction

23. Management
Diagnostic work up:-
S.TSH:-abnormally high but can be low or normal in 10% of cases
FT3, FT4
Treatment:-
Airway protection
Thyroid hormone therapy:-
 IV T4 300 mcg to 500 mcg followed by 50-100 mg/ day till patient able to take oral.
 Oral treatment is as efficacious as IV.
 T3= T4
Vivek Mathew et al, Myxedema coma: a new look into a old crisis, J Thyroid Res. 2011; 2011: 493462

24. Management
Fluid repletion
Empiric hydrocortisone
Correction of hyponatremia
Treatment of inciting factor:- empiric antibiotics

25. Thyroid storm
Preipitating factor can trigger thyroid
storm in thyrotoxic patients
1% to 2% of all hospital admissions for
thyrotoxicosis are due to a thyroid storm
More common in adolescent
3-5 times common in women
Mortality:- 20-90%

26. Clinical features
Neurological manifestations:-
Encephalopathy-----agitation, emotional liability, psychosis, confusion
Abnormal movements----tremor, choreoathetosis
Status epilepticus
Stroke
Other manifestation:-
High grade fever, sweating
GIT:- nausea, vomiting, diarrhea, jaundice
CVS:- palpitation, congestive heart failure, hypertension

27. Investigations
Leuckocytosis
Hypercalcemia
Hyperglycemia
Abnormal LFT and raised CPK
ECG:- tachyarrhythmia(AF)
CXR:- pulmonary edema or infection
Neuroimaging :- to exclude other
neurological condition
 Diagnostic work up:-
 No set serum T4 or T3 criteria exist
for diagnosing a thyroid storm.
 S.TSH:- very low
 FT3:- High
 FT4:- High to normal

28. Treatment
Supportive care:-
Control hyperthermia :- ice packs, cooling blanket and Acetaminophen
Oxygen and ventilator support
Correction of electrolyte imbalance
Treatment of cardiac arrhythmia
Antiadrenergic drug:-
To minimize sympahomimetic symptoms
Reduce conversion of T4 to T3
Propranalol----60-80 mg every 6 hourly, metaprolol or atenolol can be used.

29. Treatment
Thionamides:- inhibit new thyroid hormone synthesis
 Propylthiouracyl 200 mg every 4 hourly or methimazole 20 mg 4-6 hrly
Iodine compounds:- inhibit thyroid hormone release
Potassium iodide—5 drops every6 hours, lugol iodide 10 drops 8 hourly
Glucocorticoids:-reduce peripheral conversation
Hydrocotisone(100 mg) or dexamethasone (1-2 mg) 8 hourly

30. Treatment
Bile acid sequestrants:- prevent reabsorption
Plasmapharesis may be used rarely in adults
Treat precipitating event.

31. Hypercalcemia
Higher or rapid elevation in serum calcium levels can lead to dysfunction in
multiple organs
MC cause:- primary hyperparathyroidism
Other Causes:-
Malignancies,
Granulomatous diseases
Immobilization
Medications such as thiazide diuretics and lithium

32. Clinical features
Neurological manifestation:-
Neuropsychiatric---irritabilility, personality changes, depression
Cognitive impairment, coma
Proximal muscle weakness with bone pain
Other system manifestation:-
GIT:- nausea, vomiting, abdominal pain, pancreatitis
Renal dysfunction:- oliguria, nephrocalcinosis
CVS:- arrhythmia

33. Investigations
Hypercalcemia:- > 14 mg/dl
Raised BUN and creatinine
ECG:- PR and QRS polongation, T wave
flattening, heart block
CXR:- to rule out sarcoidosis or
malignancy
 Diagnostic work up:-
 S.PTH
 ESR
 Screen for malignancy
 Protein electrophoresis
 S.ACE

34. Treatment
Mainstay of Rx:- IV fluids---4 ltr NS in first 24 hours
Loop diuretics:- Calciuretic effect
Bisphosphonate:- patients with neurological manifestation, especially
malignancy
Calcitonin:- In acutely ill patient only
Rapid lowering of calcium but hypersensitivity and tachyphylaxis.
Glucocorticoids:- drug of choice in granulomatous disease.
Hemodialysis:- in renal failure patients

35.  A 73-year-old woman presented with a
subacute syndrome of progressive dementia
 After thyroidectomy 5 months ago
 laboratory examination revealed a
hypercalcemia of 3.25 mmol/L (normal = 2.2-
2.55 mmol/L)
After normal
calcium
Karatas H et al, Creutzfeldt-Jakob disease presenting as hyperparathyroidism and generalized tonic status
epilepticus. Clin EEG Neurosci 2007;38(4):203Y206. doi:10.1177/155005940703800404

36. Hypocalcemia
MC Cause :-acquired hypoparathyroidism
Vitamin D deficiency
Chronic renal disease
Drugs:- anticonvulsant
hypermagnesemia

37. Clinical feature
Neurological manifestation:-
Seizures
Encephalopathy
Paresthesia and perioral numbness
Choreoathetosis
Painful finger contractions ( carpopedal spasm)
Other system:-
CVS:-myocardial dysfunction and arrhythmia
 Examination :-
 Coarse hair
 Brittle nails
 Dry skin
 cataracts

38. Investigations
Hypocalcemia:-< 7.5 mg/dl
ECG:-QT prolongation
Diagnosic workup
S.PTH
RFT
S.magnesium
Vitamin D level

39. Treatment
IV calcium gluconate Bolus followed by infusion till normalize of calcium
level.
Vitamin D supplementation
Iv magnesium if hypomagnesemia present.
PTH supplement in case of hypoparathyroidism.

40. Hyperglycemia
Diabetic ketoacidosis(DKA):- Hyperglycemia + ketosis+ acidosis
Hyperglycemic Hyperosmoler State(HHS):- hyperglycemia+
Hyperosmolarity+ dehydration
Incidence:- 4-8 in 1000 patients overall, 13.4 in 1000 patients young (DKA)
Mortality :- 1% in young, 4-5 %in elderly(DKA)
upto 20% in HHS

41. Hyperglycemia
Pathophysiology:- relative or absolute insulin deficiency + Excess of
counterragulatory hormones (DKA)
Relative insulin deficiency + enough endogenous insulin to prevent lipolysis+
dehydration (HHS)
Inciting factor:- Infection---- MC
Other:- inadequate insulin dose, MI, stroke, Drugs
Additional for HHS:- immobile patient, elderly, hypnotics

42. Clinical Features
Neurological manifestation:-
Altered mental status---lethargy, coma
Seizure—Epileptia partialis continua
Hemichorea or hemibalismus
Stroke
Other systemic manifestation:-
GIT:- nausea, vomiting, abdominal pain
Renal:- polyuria---oligouria, polydipsia, thirst
RS:- respiratory distress
 On Examination:-
 Poor skin turgor
 Hypothermia or fever
 Hypotension
 Tachycardia and tachypnea
 Kussmaul respiration
 Abdominal tenderness
 Papilledema
 Pupillary changes

43. Diagnosis

44. Investigations
CBC:- leukocytosis
Electrolytes panel:- Hyperkalemia, hyponatremia, hypophosphatemia
RFT:- Increased BUN
CXR:- to r/o pneumonia or aspiration
ECG:- to r/o silent MI and detect changes of dyselectrolemia
Neuroimaging:- Effacement of Sulci, reduced basal cistern space and ventricles
size, loss of grey-white matter differentiation---cerebral edema
to rule out stroke or CVT.

45. Treatment

46. Treatment
Electrolyte correction:-
IV potassium chloride 10 meq/h
Hypernatremia:-0.45% NS or 5% dextrose
Correction of Acidosis:-
Sodium bicarbonate:- 100-150 ml (1.4%)
Treatment of concurrent illness

47. Hypoglycemia
Reduction of plasma glucose to such a level that produces symptoms.
MC endocrine emergency
Common in type 1 DM
Annual prevalence:- 7%
MC cause:- overdose of hypoglycemia agent
Other causes:- Insulinoma, Addison disease, Renal or liver failure, Infection, inborn
error of metabolism
UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities
and their duration. Diabetologia 2007;50(6):1140Y1147

48. Clinical feature
Autonomic symptoms
Sweating and palpitation
Tremors
Anxiety and sense of hunger
Neuroglycopenic symptoms:-
Weakness, Dizziness and blurred vision
Inappropriate behavior
Convulsion :- EPC, GTCS, Myoclonus
Confusion and coma
 Other system manifestation:-
 GIT:- nausea, vomiting , abdominal
cramp
 Respiratory distress
 CVS:- congestive HF

49. Clinical feature
Examination :-
Hypothermia
Tachypnea
Tachycardia or bradycardia
Hypertension
Dilated pupils
Tremors
Loss of coordination
Hemiparesis or quadriparesis

50. Investigations
 Diagnostic workup:-
 S. Insulin level
 C-peptide level
 Oral glucose tolerance test
 USG/ MRI abdomen:- to rule out insulinoma
 Neuroimaging:-
 T2 hyperintensiy with diffusion restriction can be seen
in bilateral basal ganglia, hippocampus and posterior
limb of internal capsule.
 Boomerang sign

51. Treatment
If conscious:-
15-20 gm oral glucose----200ml fruit juice or 5 TSF of sucrose in water
If reduced consciousness:-
IV 25g glucose bolus or infusion with sugar monitoring
IM or SC 1 mg glucagon ----IV not possible
Glucagon not useful in alcohol induced hypoglycemia

52. Pheochromocytoma crisis
Occurs secondary action of unopposed high
circulating levels of catecholamines
acting at adrenoreceptors
a-receptors:- pressor response with increases in
blood pressure
b-receptor:-positive inotropic and chronotropic
effects

53. Clinical features
Neurological symptoms:-
Autonomic symptoms:- Palpitations, sweating,
pallor, tremors, anxiety
Thunderclap headache
Altered consciousness
Stroke
Other system manifestation:-
GIT:- abdominal pain, paralytic ileus
CVS:- MI
 Examination:-
 Tachycardia
 Hypertension
 Papilledema and retinopathy
 Neurofibroma
 Café au lait spot
 Retinal hemangioma

54. Investigations
RFT:- proteinuria, raised BUN
2D Echo:- LVH
Neuroimaging :- s/o edema in cortical and
subcortical white matter in occipital lobe.
hypertensive bleed can be seen
Diagnostic work up:-
USG/ MRI abdomen:- for adrenal tumor and
intratumor bleed
24 hour urine free catecholamines and metanephrin

55. Treatment
Control of hypertension is main stay of treatment.
Drug of choice:- phenoxybenamine---10 mg TDS, Maximun 240 mg / day
IV phentolamine or oral prazocin
After 48 hour beta blocker can be added.
Propranalol:- 40 mg TDS
Surgical management

56. When to suspect?
Acute onset altered sensorium, status epilepticus
Hemodynamic instability:- persistent hypo or hypertension
Multiple system involvement
Examination s/o chronic endocrine dysfunction
Persistent Dyselectronemia
Normal Imaging
Not responding to treatment

57. Differential Diagnosis
SAH:- pituitary apoplexy, pheochromocytoma crisis
Stroke :- pituitary apoplexy, hypoglycemia, pheochromocytoma crisis
Hypertensive encephalopathy:- thyroid storm, Pheochromocytoma crisis
Malignant hyperthermia:- thyroid storm
CNS infection:- pituitary apoplexy, thyroid storm
Septic shock:- pituitary apoplexy, addisonian crisis, myxedema coma, thyroid storm,
DKA
Panic disorder:- thyroid storm, hypoglycemia, pheochromocytoma crisis
Acute pancreatitis or appendicitis:- DKA

58. Conclusion
Rare complication of common endocrine disorder with frequent neurological
manifestation.
Can mimic common acute neurological conditions.
Diagnosis rely on clinical presentation and evidence of endocrine dysfunction.
Role of neuroimaging is mainly to rule out other neurological conditions.
In suspected cases treatment should not be delayed till confirm diagnosis.
Prognosis is good if diagnosed and treated promptly otherwise mortality is high
upto 90%

59. References
Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management
of pituitary apoplexy. Clin Endocrinol (Oxf) 2011;74(1)
Broersen LH et al. Adrenal insufficiency in corticosteroid use: systemic review and
meta-analysis. J Clin Endocrinol Metab 2015; 100(5):2171Y2180.
UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes:
effects of treatment modalities and their duration. Diabetologia 2007;50(6)
Bradely’s Neurology in clinical practice , 7th edition
Harrison’s principle of internal medicine, 20th edition
UpToDate.com

60. THANK YOU