Case Summary:
A 36 year old married lady with 7 children & history of miscarriages who has HTN, SLE, Hypothyroid, Asthma, Epilepsy, PUD, Mitral Valve Prolapse & questionable H/O PE in 2009.

1. Hypertension:
She developed HTN in 1989 when she was only 16 Y/O. It was controlled on Atenolol. It is unclear what tests were done to rule out causes of secondary HTN. It started to be difficult to control with the diagnosis of SLE & other agents were added. She was non-adherent for extended periods of time especially the entire period between 1998 & 2003. Fundal exam was normal in 1997 but showed hypertensive changes in 2005.

I saw her for the 1st time on Oct/09 & admitted her for BP control as it was 200/130 & received one dose of long-acting Isoptin 240 & became severely hypotensive the next day requiring inotropic support. She was discharged later hypertensive on no therapy. 24 hour Ambulatory BP monitoring showed HTN most of the day with night dips. She was started on Diovan 160 & Norvasc 10 but according to her, BP remained very high most of the time.

She was admitted on Dec/09 in shock (BP 80/50) while on same therapy & required inotropes & IV fluids. Cardiac markers were normal, blood cultures were negative, & Hb, K, Ca, Na, Mg, TSH, FT4 were all normal. She was in CCU for 3 days & was continuously monitored & had no evidence of arrhythmias. BP became very high a few days later & was started on therapy (Aldomet, Adalat, Aldacton) with no response. She was put on Isoptin 40 TID but that caused severe symptomatic hypotension. She was put on Aldomet & Prazosin, but that failed to control BP. She was later put on Diovan (80) & co-diovan (80) morning & Diovan (160) afternoon & cardura (4) & Aldacton (100) noon & evening without any effect on her BP. This complicated dosing regimen was to avoid severe hypotension.

We also tried her on moxonidine (selective imidazoline against acting on CNS to decrease sympathetic outflow) as an alternative to clonididne & in addition to other medications without success. She was also put on moduretic (Amiloride 5 mg & hydrochlorothiazide 50 mg) for the remote possibility of Liddle’s syndrome without any success & it was in combination with minoxidil.

Each combination was tried for several weeks before declaring failure of that combination & we are still trying, however, our efforts are hampered by hypotensive crisis.

Hydralazine in large doses & in women can infrequently induce lupus-like state so we stopped it. Anyways, it did not help in BP control. Methyldopa can also cause the same problem so we stopped it, especially it also failed to control BP (in addition to other drugs). However, patient was taking both drugs for a while & did not influence SLE serology.

β-Blockers are contraindicated because of her asthma although she was on it in the past before acquiring asthma & the chest physician advised against ACEI use because the cough it may induce can exacerbate or complicate her asthma. However, we put her on labetalol 200mg Bid, which was the maximum dose she could tolerate because of her asthma (in addition to other medications) & it did not control her BP. We also put her on ACEI

2-SLE
In 1993, she had thrombocytopenia with normal bone marrow biopsy. So she was diagnosed with ITP & was treated with steroids, but not sure for how long. In 97 she developed arthralgia & hair loss & found to have anemia/thrombocytopenia with positive ANA/Anti ds DNA. So she was diagnosed with SLE +/- Sjogren’s syndrome & was treated with steroids & imuran. Again, I am not sure from her file duration of therapy & response. However, ANA, Anti ds DNA, ACL/β2GP, protein C&S, Anti ENA (SSA, SSB, SM, RNP, SCL-70, anti-JO 1) were done in 03, 04 & 09 and were negative together with normal C3/C4 & negative Coomb’s test. She is off therapy, although takes a small steroid dose for asthma. Tonsillectomy done in 85, at age 15, possibly due to recurrent tonsillitis with arthralgia.

3-Pulmonary Embolism:
This was suspected on Mar/09 when she was admitted with SOB & palpitations. V/Q scan showing intermediate probability. She was started on warfarin. CT angio was not done at that time, but was normal on Aug/09. She stopped anticoagulation by herself & I am not sure of the accuracy of the diagnosis & I am not sure if it is wise to restart anticoagulants with such poorly controlled severe HTN. She had an episode of epistaxis in Jan/2010 & refused admission. She had normal Protein C, Protein S & Antithrombin & negative Anti-Cardiolipin antibodies & negative anti-β2 Glycoprotein.

4-Bronchial Asthma
She is on seretide with infrequent exacerbations. She is on Prednisolone 10mg OD & does not want to cut it down. She had an episode of acute exacerbation in Jan/2010 requiring hospitalization for Nebulizers & IV steroids.

5-Hypothyroidism
She had total thyroidectomy on Aug/09 apparently for failure of medical therapy to control thyrotoxicosis including radioactive iodine. She was admitted on Mar/09 for thyroidectomy but BP was high (150/110) despite therapy (Aldomet 500 TID, dilatrend 6.25 BID, Capoten 50 BID & prazosin 2 BID), so she was given Isoptin (90 TID) but became severely hypotensive, with 1st & then 2nd degree heart block (she was on Digoxn in addition to Dilatrend) & managed by inotropes. She was hypokalemic (2.8-3.3) D/T low magnesium, both were corrected. Apparently the Digoxin was to control her heart rate.

6-Epilepsy:
She has been diagnosed with epilepsy since 1998 while pregnant (not sure if it was D/T SLE exacerbation or pre-eclampsia). She had normal head CT & MRI. She also had normal EEG in Jan/2010. She is maintained on Keppra & Depakane. She says she gets what she described as fits when her BP becomes very low at home, but not sure if her description fits the true description of seizures or just convulsive syncope.

7-PUD:
UGIE was done in 2010 & showed GERD with oesophagitis & gastritis. She is on Losec.

8-Mitral valve prolapse:
This was diagnosed by echo in 07 & when echo was repeated in 09 it also showed septal hypertrophy with EF of 55%. Echo was repeated in UK in 2010 &showed dilated LV with reduced EF to 45%, suggesting hypertensive dilated cardiomyopathy.

She reported several episodes of symptomatic hypotension at home & she presented on Jan/2010 with severe hypotension, again requiring inotropes for 36 hours & then she became hypertensive again.

She says that episodes of hypotension started only in late 2009 & in some occasions happened without any therapy (i.e. when she stopped taking therapy). Hypotension is definitely not orthostatic, but may be accompanied by convulsive syncope according to her description. Again, according to patient, episodes of hypotension vary in severity & duration & are not related emotions or situation (i.e. micturition, cough)

We are faced with 2 problems that complicate each other & these are the resistant HTN & the paroxysmal severe hypotension (with or without therapy).

A-Resistant HTN:
This is definitely not white coat HTN & not due to improper BP measurement as she checks it at home & had 48hr ABP monitoring. It is also not pseudo-hypertension as this young, thin & non-diabetic lady does not have heavily calcified arteries. She has no evidence of volume overload & no evidence of obstructive sleep apnea (in fact, BP drops a little at night according to ABP monitoring). There is also no H/O ingestion of Alcohol, street drugs, sympathomimetics (decongestants), licorice, over-the –counter herbal remedies (ginseng, yohimbine), OCP, or other drugs that can raise BP such as NSAIDs, Cyclosporine, Tacrolimus, or Erythropoietin.

I am not sure if the small dose of steroids is contributing to her uncontrolled HTN. In fact, steroid dose was increased significantly for acute exacerbation of asthma & did not influence her BP control, in case it was gluco-corticoid – remediable hypertension.

Non-adherence plays a partial role & I do believe that psycho-social element is involved but was refusing formal psychiatric assessment or medication for that. She has been diagnosed with some sort of psychiatric illness like anxiety or depression in the past but no formal psychiatric diagnosis was made & she was on no therapy for that. She says she sought the advice of psychiatrist in private clinic in the past & drugs were prescribed that helped her BP but she did not like the drugs side effects & stopped it. We prescribed the antidepressant, parozetine with small dose of benzodiazpines in an attempt to treat pseudopheochromocytoma. She states she is adherent, however, no effect is seen on BP at all.

Investigations for secondary HTN:
a) – Normal renal function & no evidence of renal artery stenosis by us & MRI
b) – No adrenal lesion on abdominal MRI & US & negative MIBG twice in /Kuwait & twice in UK. & CT in UK.
c) – Normal potassium & treatment with Spironolactone did not affect BP
d) – Normal 24h urine for catecholamine & metanephrine & normal 5H1AA
e) – Normal plasma rennin, aldosterone, catecholamines & fasting plasma cortisol & ACE
level
f) - Negative serology for immune disorders (C3/C4, ANA & Anti DNA, ANCA) &
Hepatitis
g) – Normal thyroid (on replacement therapy) & parathyroid functions

For the above mentioned HTN problem, the patient report was sent to BUPH cromwell Hospital, UK and she traveled there on June 2010 and fully investigated for her HTN problem there was no new in her investigations in comparison to what was done in Kuwait except for a positive VMA level and abnormal metanephrines. Those findings suggested pheochromocytoma. She was initiated on phenoxybenamine 10mg titrated over 3 months to reach 70mg ten day added to Diovan 160mg but unfortunately no benefit regarding BP control or hypotensive episodes.

B- Paroxysmal Hypotension:
Autonomic dysfunction (such as pure autonomic failure or multiple system atrophy) was suspected but autonomic function tests were negative (such as table-tilt, hand grip ratio, metronomic breathing test, etc,.). The other possibility is occult pheochromocytoma despite negative MRI, MIBG & blood tests. One remote possibility is that she does not take her medications without telling us so we increase the number & dose of medications & when she takes these drugs given for severe resistant hypertension, she becomes hypotensive.

Current therapy:
- Diovan 160mg OD
- Co-Diovan 160 mg OD
- Norvasc 10mg OD
- Eltroxin 200mg PO OD
- Keppra 1 g BID
- B.Aspirin 81mg PO OD
- Lipitor 20mg PO OD
- Losec 20mg PO OD
- Prednisolone 10 mg PO OD
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