A case of a patient with pulmonary hypertension associated with multiple endocrine dysfunctions and connective tissue disorder

PVRI Member Authors: Mrigendra Bastola, Salina Gairhe


 Pulmonary hypertension in association with connective tissue disorders, thyroid dysfunctions and hyperestroginism has been reported. However, the presence of pulmonary hypertension in multiple endocrine dysfunctions (i.e. pituitary adenoma, endometriosis and ovarian cysts, thyroid dysfunction) with connective tissue disorder has rarely been described. This is a case of the coexistence of pulmonary hypertension in a patient with functional pituitary adenoma, thyroid cysts and goiter with endometriosis and connective tissue disease with a diagnostic difficulty faced in presence of long standing bronchial asthma. The case illustrates the association of pulmonary hypertension in the setting of endocrine dysfunctions and connective tissue disease, and the effect on its course.

The case

 This is a case report of 42 year old Hispanic female (Figure 1), who with gradually increasing shortness of breath approached our research team asking for medical help at the Pulmonary Hypertension Association conference in Florida, 2012. Our team’s first impression of this case was a bronchial asthmatic patient who suddenly got dyspneic.

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Figure 1: PAH patient

 Upon further questioning, we found that she had shortness of breath since her childhood and was taking inhaled bronchodilators occasionally. During conversation, she described having repeated headaches and occasional visual disturbances during her twenties. On the sixth year of medications for migraine, her life changed with a sudden onset of bitemporal vision loss. She narrates, “I was treated in the Puerto Rico for about 6 years, because I was experiencing heavy headaches that the doctor “mistook” or “confused” with migraines, and I was recommended to take Acetaminophen/ Isometheptene/Caffeine tabs, and later told to use Acetaminophen/ Butalbital/Caffeine. As the headaches did not subside with these medications, I consulted my endocrinologist and she ordered a brain MRI.” When she was 26, she underwent a MRI which showed a pituitary adenoma (Figure: 2, Pituitary Adenoma (A)Coronal and (B)saggital views), which was functional. She was then treated with Bromocriptine and Cabergoline 0.5 mg two tablets a week. With this treatment, her prolactin levels in serum remained high, however, the tumor regressed in next two years, and symptoms improved. At that time, she had never thought that another turn in her life was coming with a rash on her malar area.

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Figure 2: Pituitary Adenoma (A) Coronal and (B) Transverse views.

She had occasional bones and joint pains too in the past and was investigated for joint disease. She was found rheumatoid factor positive in her 27th year, but no attention was given to her connective tissue disease until her 29th year when her tests for Systemic Lupus Erythematous (SLE) came out positive. That is when proper treatment of the SLE and joint pain was started. She explains, “My SLE was discovered in 2004. The usual treatment for my SLE was Prednisone tablets and the dosage ranged from 5mg to 80mg or 125mg a day, depending on, whether I have a flare up or not. I used Prednisone 200mg tablets two times a day and the chemo Methotrexate Injections subcutaneous weekly. I also had Rituximab 1,000mg infusions every two to three months for almost 3 years. I stopped the Rituximab infusion treatments and the Methotrexate weekly injections and the Prednisone due to recurrent skin and blood bacterial infections. I did not start them again until my recurrent infections were stable. 

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Figure 3: Oral lesions and Malar Rash during SLE Flare up

If I had a flare up, I use the Prednisone treatment.” (Figure 3) With no remission in the past and after ten years of SLE treatment, she developed progressive worsening of shortness of breath which she had since her childhood. Her chest X-ray showed normal findings. With high suspicion of pulmonary hypertension associated with SLE, an echocardiogram was performed to analyze the condition of her heart. Based on its findings, she was diagnosed with pulmonary hypertension for the first time. When she was 37, anticardiolipin antibodies were sent which came out positive. At 40 years of age, she was diagnosed with having multinodular goiter on basis of her ultra-sonogram of thyroid and thyroid function tests (Figure 4).

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Figure 4: Multinodular Goitre: please see text for further information

In her own words, she says “My PAH was discovered on an echocardiogram on November of 2009, but I started my treatment on January 2010 with the Bosentan 62.5mg, then the dosage changed to 125mg two times a day. On February of 2010, I started the Sildenafil 20mg tablets three times a day. I also used a diuretic Hydrochlorothiazide 50mg daily to manage fluid retention.” The diagnosis of pulmonary hypertension was confirmed by right heart catheterization, with pressure of more than 50mmHg. The bronchoscopy and pulmonary biopsy showed an enlarged carina and inflammation, and her right heart catheterization showed elevated baseline pressure. Pulmonary function tests with measurement of forced vital capacity (FVC) and diffusion capacity of CO (DLCO) were also performed, and showed a ratio of more than 1.6, favoring her dyspnea because of the pulmonary hypertension to the restrictive pathology of her lungs, due to the connective tissue disorder (Figure 5). 

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Figure 5: Pulmonary Function Tests: please see text for further information

“Past medical conditions before my diagnosis of SLE ….”, she exhales deep and tells that she had too many surgeries and biopsies since adolescence, including those for ovarian cysts and endometriosis. Except for the maxillofacial surgery for torus mandibularis on both jaws and cordialis surgery when she was 12 years old, tonsillectomy for bilateral recurrent tonsils infection at 6 years old, and admission for supracondylar fracture of the right, her school health was unremarkable and she believed herself to be in a good health. However, when she was 14 year old, she underwent abdominal laparoscopy to remove ovarian cysts, which was unsuccessful for technical reasons (Figure 6). 

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Figure 6: Ovarian Cysts

At the age of 22, she was operated for pilonidal cyst and this cyst changed into chronic draining sinus for 6 months. One year later she underwent another surgery for spinal cyst and draining pilonidal sinus. She was also diagnosed with colon polyps and colon hyperplasia by a gastroenterologist at the age of 21, which were successfully removed. When she was 24, she was diagnosed with endometriosis, and ovarian cyst in the same setting. She had rectal bleeding which was treated with superficial mucosal laser erosion at 29. She developed irregular menstrual bleedings, and underwent dilatation and curettage. The biopsy reports showed dissociation of stromal and glandular elements.


With the rising incidence of PAH patients and associated debilitation, it is necessary to consider every possible past clinical pathology as a possible trigger for PAH. In every case of dyspnea in connective tissue disease, the probability of pulmonary hypertension should be actively sought as in this case, where proper management could be done in a timely manner. Furthermore, it is absolutely necessary to manage both SLE and bronchial asthma side by side since SLE flares pulmonary hypertension and bronchial asthma would not only hide the progress of pulmonary hypertension, but also make symptoms of the heart failure worse. This case also points to the positivity of rheumatoid factor and anticardiolipin antibodies which served as a guide to investigate pulmonary hypertension associated with SLE1 , though further studies need to be done on their sensitivity and specificity and thereby relevance of their prognostic use in future. The dyspnea becomes favorable with predominance of pulmonary hypertension, if the ratio of FVC/DLCO is more than 1.6, than with the restrictive pathology because of the connective disease, owing to the fact that the fall in DLCO will be much higher than FVC.

In this case, even in a midst of diagnostic difficulty with symptoms of bronchial asthma, a diagnosis was made. After making a relatively early diagnosis, the case was treated with Bosentan, Sildenafil and Thiazides and her symptoms have decreased to NYHA grade 2 dyspnea. Her pulmonary arterial pressure has decreased from 55mmHg to 36mmHg. Another option available for the management of a case like this is IV prostacyclin, although if prescribed, its potential complications like infection of the central venous site should be properly explained to the patient. In addition, the patient’s ability to store the drug properly in refrigerator and its preparation on a daily basis should be considered. In a case like this, where the symptoms of bronchial asthma hid the early manifestations of pulmonary hypertension, constant vigilance is essential, with proper screening modalities like echocardiogram and six minute walk test.

 Pulmonary hypertension has been linked with autoimmune thyroid diseases and hyperthyroidism.2 Nevertheless, as in this case, we might encounter pulmonary hypertension with hypothyroidism. Thus thyroid function tests should be sought, especially if the patient is over sixty years old.

This case may illustrate the issue of the association of pulmonary hypertension with multiple endocrine dysfunctions, which also should not be overlooked. The association of pulmonary hypertension with abnormalities in metabolism of insulin, adipokines, estrogen and lipids have already been suggested by research.3 For our patient, the presence of pulmonary hypertension with multiple endocrine dysfunctions is highlighted. The association of high incidence of pulmonary hypertension in females had been previously attributed to the presence of estrogen, especially if it is in high levels with early and long term exposure.4 The rare associations of pituitary adenoma, polycystic ovarian syndrome, endometriosis and multinodular goiter in a same case suggest pulmonary hypertension might have precipitated and/or aggravated multiple endocrine dysfunctions, which is particularly important in current research of pulmonary hypertension as hormones such as estrogen, progesterone and thyroid have been linked to the disease’s course.


 In this case study, an association of pulmonary hypertension with bronchial asthma, systemic lupus erythematous and multiple endocrine dysfunctions is highlighted. Though systemic lupus erythematosus with high titers of rheumatoid factor and anticardiolipin factor have been associated with pulmonary hypertension, its association with other endocrine syndromes in concert suggests it could be a part of multiple endocrine dysfunctions as well, including dysfunctions of the pituitary gland.



1. Kamel SR, Omar GM, Darwish AF, Asklany HT, Ellabban AS. Asymptomatic pulmonary hypertension in systemic lupus erythematosis. Clin Med Insights Arthritis Musculoskelet Disord. 2011;4:77-86. doi: 10.4137/ CMAMD.S7667. Epub 2011 Sep 28.

2. Marvisi M, Balzarini L, Mancini C, Mouzakiti P. Thyroid gland and pulmonary hypertension. What’s the link? Panminerva Med. 2013 Mar;55(1):93-7.

 3. Meredith E. Pugh, M.D. and Anna R. Hemnes, M.D. Metabolic and Hormonal Derangements in Pulmonary Hypertension: From Mouse to Man Int J Clin Pract Suppl. 2010 November; 64(168): 5–13.

 4. Sweeney L, Voelkel NF. Estrogen exposure, obesity and thyroid disease in women with severe pulmonary hypertension. Eur J Med Res. 2009 Sep 28;14(10):433-42. 


Pulmonary Hypertension

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June 2014

PVRI Chronicle Vol 1: Issue 1

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