CE - LETTER TO THE EDITOR

An unusual case of dilated cardiomyopathy associatedwith partial hypopituitarism

Alberto Maria Marra • Michele Arcopinto •

Emanuele Bobbio • Andrea Salzano •

Luigi Sacca • Antonio Cittadini

Received: 22 February 2011 / Accepted: 14 June 2011 / Published online: 29 June 2011

� SIMI 2011

Dilated cardiomyopathy (DCM) secondary to endocrino-

logic disease occurs rarely. In a large clinicopathological

review of 673 patients, only 1.5% fall in the metabolic

category, mostly due to thyroid disorders [1]. Sporadic

reports of DCM associated with other endocrinopathies

have been subsequently published including acromegaly,

GH deficiency, pheochromocytoma, hypoparathyroidism,

Sheehan syndrome, and Addison’s disease.

We herein describe a rare case of DCM secondary to

partial hypopituitarism, in turn related to a previous intra-

cranial surgery, promptly responding to multiple hormonal

replacement therapy.

A 55-year-old woman was admitted to our Intensive

Coronary Unit in February 2008 because of a community-

acquired pneumonia complicated by acute heart failure.

Her chief complaint was shortness of breath, which had

become progressively worse during the prior 4–5 days. She

had a productive yellow cough and blood-tinged sputum.

Examination revealed a tachycardia (115 bpm), tachypnea

22 breaths/min, BP 90/50 mmHg, a raised venous pressure,

fine bilateral basal crepitations, right-sided crackles, and

dullness to percussion. She was treated conventionally in a

territorial hospital for acute pulmonary edema with partial

initial symptomatic recovery. The patient was also

started on a ‘‘pneumonia protocol’’ with cefotaxime and

azithromycin, and oxygen. Notwithstanding standard ther-

apy for acute heart failure including nitrates, furosemide

and digoxin, and the introduction of inotropic support, the

patient was still hypotensive, and for this reason she was

admitted to the intensive care unit of our tertiary care

hospital. The past medical history revealed systemic

hypertension, chronic kidney disease (GFR of 25 ml/min),

subclinical hypothyroidism (TSH 6.3 lU/mL with normal

FT3 and FT4), and surgical intervention for aneurysmec-

tomy of the left middle cerebral artery, which had been

performed in 2006. She never smoked or used alcohol

EtOH or drugs. She lived with her family.

A complete mono-two-dimensional and Doppler echo-

cardiographic examination was performed. The ultrasound

analysis displayed a very enlarged poorly contracting left

ventricle (EF 13%) with moderate-to-severe mitral regur-

gitation (see Fig. 1; Table 1). Diastolic function was

moderately impaired. Interestingly, a previous echocar-

diogram obtained in 2006 was reviewed, and only dis-

played mild LV hypertrophy with normal cavity diameters

and a preserved systolic function (EF 55–60%).

After resolving the decompensated HF and the right

pneumonia, the patient was still in class IV of the NYHA,

and could not undergo a cardiopulmonary stress test that

we routinely perform in CHF patients. To rule out ischemic

etiology, a coronary angiography was performed that

revealed no significant coronary stenosis. An endomyo-

cardial biopsy was suggested but not performed since the

patient refused the procedure.

A complete hormonal panel showed low levels of early-

morning serum cortisol and undetectable levels of serum IGF-

1 without evidence of secondary gonadal failure (Table 1).

Thyroid failure was partial insofar as TSH increased up to

10.9 lU/mL, indicating residual pituitary secretion. We next

performed a GHRH ? arginine stimulation test for diagnosis

A.M. Marra and M. Arcopinto contributed equally to this work.

A. M. Marra � M. Arcopinto � E. Bobbio � A. Salzano �L. Sacca � A. Cittadini

Department of Clinical Medicine and Cardiovascular and

Immunological Sciences, University Federico II, Naples, Italy

A. Cittadini (&)

Department of Internal Medicine and Cardiovascular Sciences,

University Federico II, Via Sergio Pansini 5, 80131 Naples, Italy

e-mail: antonio.cittadini@unina.it

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Intern Emerg Med (2012) 7 (Suppl 2):S85–S87

DOI 10.1007/s11739-011-0649-9

of acquired GH deficiency. A CT scan of pituitary region did

not show significant morphologic alterations. No evidence

was found of diabetes insipidus.

On top of optimized therapy for CHF that included beta-

blockers, loop diuretics, CEI, nitrates, and low doses of

aldosterone receptor antagonists, we added the following

hormone replacement therapy: cortisone acetate 37.5 mg/day

and levotyroxin 12.5 mg/day for the first 30 days and then

25 mg/day. After 2 weeks, recombinant human GH (rhGH)

was started at the replacement dose 0.25 IU/kg/week. The

patient was re-evaluated after 6 months, and showed a

remarkable improvement of clinical status and cardiovascular

performance. She gained weight, approximately 2–3 kg,

NYHA class shifted from IV to I, BP rose to 110/80 mmHg,

and GFR increased from 25 to 50 ml/min. The hormonal

profile displayed the normalization of the main axes as

depicted in the table. Echocardiography detected a dramatic

increase of both systolic and diastolic function. Cavity

dimensions decreased accordingly, and particularly impres-

sive was the change in the end-systolic LV volume (see

Fig. 1). Cardiopulmonary stress test was performed, and the

patient displayed a markedly improved performance.

The current case represents a very unusual DCM with

severe symptomatic CHF in a patient with hypopituitarism

promptly responding to multiple replacement therapy. The

peculiarities of the case report are many and include the

following:

Fig. 1 Transthoracic echocardiography performed at baseline and after 6 months of hormone replacement therapy

Table 1 Echocardiography, cardiopulmonary exercise testing and

hormones at baseline and after 6 months of therapy

Baseline After

6 months

Heart rate (bpm) 110 80

Systolic/diastolic blood pressure (mmHg) 90/50 110/70

End-Systolic volume (mL) 128 63

End-Diastolic volume (mL) 148 103

Ejection Fraction (%) 13 38

E/A ratio 1.57 0.82

E/E0 19 4.7

TSH (lU/mL) 10.9 7.63

FT3 (pg/mL) 1 1.6

FT4 (ng/dL) 0.27 0.42

Early-morning cortisol (lg/dL) 9.98 27.2

IGF-1 (ng/mL) Unfeasible 140

ACTH (pg/mL) 9.88 20.1

Maximal oxygen consumption (ml/kg/min) Unfeasible 14.4

Workload (watt) Unfeasible 39

S86 Intern Emerg Med (2012) 7 (Suppl 2):S85–S87

123

(1) to our knowledge this is the first case of partial

hypopituitarism associated with dilated cardiomyopa-

thy, insofar as all previously reported cases only describe

cardiomyopathies following panhypopituitarism;

(2) although hypopituitarism of various degree may

develop in patients undergoing neurosurgery even

far from hypothalamic–pituitary region, most diseases

occur following excision of primary brain tumors and

not because of aneurysmectomy;

(3) the response to the replacement therapy was impres-

sive, to a larger extent than reported so far;

(4) at variance with previous reports, we started almost

simultaneously glucocorticoid, thyroid, and GH

replacement therapy, and the GH dose was lower.

The most likely explanation for the hypopituitarism is the

previous intracranial surgery. Indeed, Ghigo et al. [2] report

that hypopituitarism of various degrees may develop 1 year

after neurosurgery even in areas far from the hypothalamic–

pituitary region because of the particular fragility of these

structures. Most cases were secondary to primary brain

tumors, and the incidence of hypopituitarism is 43.2%.

Very few cases have been described so far linking

hypopituitarism to dilated cardiomyopathy. Cuneo et al. [3]

describe a case of a 53-year-old man in whom a total

hypophysectomy was performed for Cushing’s disease.

Then Frustaci et al. [4] describe a case of a 49-year-old

woman with clinical and biochemical signs of panhypopi-

tuitarism who presented with severe DCM. Fazio et al. [5]

report a case of CHF in a 48-year-old woman with a history

of hypopituitarism treated only with partial replacement

therapy. While the interaction between the GH/IGF-1 axis

is well recognized, the role of chronic hypothyroidism in

the development of severe heart failure is less often

described. Most cases of acute hypothyroidism in fact

mimic acute coronary syndromes rather than dilated

cardiomyopathy.

We are aware that association of partial hypopituitarism

and dilated cardiomyopathy does not imply a causal rela-

tionship. In this regard, we cannot exclude that the standard

therapy for CHF significantly contributed to the cardio-

vascular improvement of our patient. Doubts also remain as

to which of the hormone replacement therapies had the

major impact on the cardiovascular system.

Conflict of interest None.

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