Note:  This case comes from Hospital Regional, one of the 3 main public hospitals in Cusco.  More to come about these different hospitals later.

HPI:  60 yo male who is a poor historian is referred to Hospital Regional from a local clinic for a diagnosis of pulmonary tuberculosis with a worsening progression.  The patient noted a 2 month progression of dry cough and sore throat, for which he went to a local clinic.  At the clinic, he was diagnosed with pulmonary tuberculosis based on a sputum stain positive for acid-fast bacteria.  The patient was started on an unknown medical regimen, but his clinical progression worsened and he began to also have diarrhea with nausea/vomiting.  At that point the patient was referred to Hospital Regional and admitted on Oct. 10, 2011 for further work-up and management.

PMHx/PSHx:  No significant past medical or surgical history

FHx:  Mother and Father have deceased due to unknown reasons.  His wife is 60 yo, apparently healthy.  He has 2 sons, both also apparently healthy.

SHx:  From Paucartambo, a town in the region of Cusco.  He speaks quechua and Spanish.  He works in agriculture.  He lives in an adobe house with his wife, which has 2 rooms.  His economic status is poor.  He denies any recent sick contacts or exposure to tuberculosis.

Physical Exam:
Vital Signs:  T – 97.7  BP – 90/60  P – 70  R – 24  O2 Sat – 89%  Wt. – 96.8 lbs
Gen:  Appeared thin, frail, cachectic, disheveled.  Some respiratory distress was apparent.
HEENT:  Pupils equally reactive and round to light with accommodation.  No oral lesions, pharynx/tonsils are within normal limits.  No nasal discharge.  No evidence of blood or sputum in the oropharynx.
Chest:  Thorax appears frail with ribs noticeable.  Some hyperresonance was found on percussion and diffuse ronchi were auscultated in all lung fields.  A systolic 3/6 murmur was also noted in the mitral area, non-radiating.
Abd:  Soft, non-tender, scaphoid, bowel sounds present.  No hepatospleenomegaly.
Circulation:  No evidence of JVD, skin turgor within normal limits, capillary refill < 2 seconds.
Skin:  No obvious lesions or deformities, appears tan.  No evidence of cyanosis.
Ext:  No edema or tenderness, no visible lesions or rashes.   No clubbing of fingers.

Brief Differential Diagnosis:
-Pulmonary Tuberculosis
-Pneumonia – Bacterial
-Pneumonia – Viral
-Atelectasis
-Bronchiectasis
-Lung Abscess
-Congestive Heart Failure

Hospital Progression:

10-11-11:  Patient was admitted to Hospital Regional with a preliminary diagnosis of pulmonary tuberculosis based on sputum stain.  Records from previous clinic were not available.
Therapy:
-Patient started on RIPE therapy:  Rifampin 440 mg, Isoniazid 220 mg, Pyrazinamide 1100 mg, Ethambutol 880 mg
-Prophylactic ranitidine started
-Diphendydramine started
-NaCl solution
Tests:
-Chest X-ray ordered
-Sputum Culture sent
–HIV test ordered, results negative
-Abdominal Ultrasound ordered, showed mild liver disease
-Basic Metabolic Panel (BMP) and Complete Blood Count (CBC) ordered:
Glu – 49, Urea – 22, Cr – 0.9, Alk Phos – 253, HCT – 32%, WBC – 11,000

Patient's CXR consistent with pulmonary tuberculosis

Close-up of patient's right lobe

Close-up of patient's left lobe

10-13-11:
Tests:
-6:00 am glucose was ordered – 84
-Another BMP was sent:
Na – 107, K – 3.0, Cl – 97, Bicarb – 22.3
-Arterial Blood Gases (ABG) were sent:
pH 7.42, pC02 – 35, pO2 – 56

10-14-11:
Therapy:
–Hydrocortisone 80 mg q8hrs was started

10-16-11:
Tests:
Another BMP was sent:
Na – 127, K – 3.2, Cl – 106, Bicarb – 23.1
-Another ABG was sent:
pH 7.4, pC02 – 37, pO2 – 71

10-17-11:
Therapy:
-Prednisone 20 mg q24hrs was added to regimen

Case Discussion:
A final diagnosis of pulmonary tuberculosis was made based on the patient’s signs and symptoms, and confirmed with a positive sputum stain for acid-fast bacteria.  Upon admission to the hospital, a CXR, sputum culture, and HIV test were ordered as part of an appropriate work-up.  As there was no suspicion of drug resistance, the patient was started on the standard first-line regimen for tuberculosis, RIPE therapy (Rifampin, Isoniazid, Pyrazinamide, and Ethambutol).  Tuberculosis should never be treated with a single drug, and the 4 drug combo of RIPE is appropriate for cases of drug-susceptible TB.  The minimum length of treatment for drug susceptible TB is 6-9 months.   There are 2 phases of treatment for patients with TB—the initiation phase (bactericidal or intensive phase), which consists of 2 months of therapy, and the continuation phase (subsequent sterilizing phase), which lasts 4 to 7 months for patients with drug-susceptible disease.  The 4 drug RIPE combo is used in the first 2 month initiation phase, and then pyrazinamide and ethambutol and discontinued, while isoniazid and rifampin are continued for the next 4-7 months in the continuation phase.

List of first-line therapy drugs for drug-susceptible tuberculosis, along with common side effects.

Algorithm for initiation and continuation phase of tuberculosis treatment.

Our patient was appropriately started on the correct anti-tuberculosis treatment and has begun the initiation phase.  However, upon checking some initial labs upon his admission, it was found that he was hypoglycemic with a glucose of 49.  To follow-up with this lab, some basic electrolytes were ordered the next day, including a sodium and potassium.  His sodium came back at 107, severe hyponatremia.  It has been reported that approximately 11% of patients with active tuberculosis are affected with hyponatremia (Chung et al., 1969), and it is known that the major cause of hyponatremia in patients with tuberculosis is syndrome of inappropriate antidiuretic hormone (SIADH) (Cockcroft et al., 1976).  However, because our patient also was presenting with hypoglycemia in addition to hyponatremia, and also had clinical symptoms (e.g. nausea, vomiting) a diagnosis of adrenal insufficiency was made based on clinical suspicion.  Primary adrenal insufficiency is usually confirmed by measuring an early morning cortisol level, or using a stimulation test with adrenocorticotropic hormone (ACTH).  However, neither of these tests were available in the hospital, nor the ability to measure for ADH.  Furthermore, as the patient’s clinical progression improved after the initiation of hydrocortisone, the clinical diagnosis of adrenal insufficiency was further supported.  While primary adrenal insufficiency  (Addison’s Disease) in the United States is most often caused by an autoimmune dysfunction, in developing countries, the most common cause is Tuberculosis.

References:
1.  Blumberg HM, Leonard MK, Jasmer RM.  Update on the Treatment of Tuberculosis and Latent Tuberculosis Infection.  JAMA. 2005;293:2776-2784.
2.  Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C. Tuberculosis. Lancet. 2003;362:887-899.
3.  Chung DK, Hubbard WW. Hyponatremia in untreated active pulmonary tuberculosis. Am Rev Respir Dis 1969;99:595–7.
4.  Cockcroft DW, Donevan RE, Copland GM, Ibbott JW. Miliary tuberculosis presenting with hyponatremia and thrombocytopenia. Can Med Assoc J 1976;115:871–3.